Effects of atmospheric suspended particulate matter on the immune system

Year & Volume - Issue: 
Elena V. Kondratyeva, Tatyana I. Vitkina
Article type: 
PDF File: 
Atmospheric pollution causes enormous damage to public health worldwide resulting in millions of deaths annually, and reducing both life expectancy and quality of life. Suspended particulate matter (SPM) in the air triggers immune system responses, which in turn determines a wide range of diseases based on chronic inflammation. However, many issues regarding the relationship between air pollution and the development and course of pathologies remain unresolved. The present review summarizes the data of domestic and foreign publications regarding the effect of atmospheric SPM on the immune system. The article reveals the effect of SPM on immunocompetent cells and investigates cellular and molecular response mechanisms of the body. The data presented in the review imply the need for further studies of immune system response mechanisms under the impact of atmospheric SPM.
Cite as: 
Kondratyeva EV, Vitkina TI. Effects of atmospheric suspended particulate matter on the immune system. Russian Open Medical Journal 2024; 13: e0103.


According to the World Health Organization (WHO), air pollution causes enormous damage to public health worldwide resulting in millions of deaths annually, and reduces life expectancy and quality of life [1]. Suspended particulate matter (SPM) is a heterogeneous mixture of solid particles of different sizes, qualitative traits and quantitative characteristics. The chemical composition of SPM can be represented by nitrates, sulfates, carbon, organic and biological compounds, along with various metals (iron, copper, nickel, zinc, etc.) [2, 3]. The main area of exposure to SPM when inhaling ambient air is the respiratory tract from the nasal passages to the lungs, where direct interaction between particles and cells of the respiratory tract occurs. Microtoxicants in the ambient air activate immune system responses, which, in turn, determines a wide range of diseases with underlying chronic inflammation [4-8]. SPM triggers signaling pathways leading to the activation of a complex response of the immune system, including the participation of various types of cells [9-12]. This field of study is of great interest to researchers. Numerous publications are presented in foreign and, to a lesser extent, Russian scientific journals. They are usually devoted to identifying the response of immunocompetent cells and cytokines to SPM. Our review summarizes ideas about response mechanisms at several hierarchical levels: from cellular to molecular. The interaction of the immune system with thiol-disulfide homeostasis in the formation of a response to air microtoxicants are shown. Abnormalities in subpopulations of immune cells that signal dust particles are described in detail. The features of the immune system’s response to different qualitative compositions of SPM are presented.


Impact of SPM on immunocompetent cells

Airway epithelial cells (ECs) are the most important target for inhaled SPM because they are the first barrier to xenobiotics, capable of releasing various mediators [13]. In response to the detection of microtoxicants, human bronchial epithelial cells produce a variety of cytokines, chemokines, and other signaling molecules, including interleukins (IL-1α, IL-1β, IL-6, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF), which contribute to the activation of airway inflammation (Figure 1) [9, 14]. IL-6 content are of particular importance when exposed to SPM. Increased SPM contamination has been shown to result in a concomitant increase in IL-6 levels in airway epithelial cells, macrophages and bronchoalveolar lavage fluid, as well as in the systemic circulation [9, 15, 16]. Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the maturation of myeloid dendritic cells (DCs) and the differentiation of monocytes into DCs, and is required for the survival of granulocytes [9, 17]. The functions of these cells are cross-linked: ECs can control DC function by secreting cytokines that stimulate a Th2 response [18].


Figure 1. Effects of SPM on immunocompetent cells.


Dendritic cells of the human respiratory tract form complex adaptive immune responses when interacting with SPM. DCs form the link between innate and adaptive immunity by recognizing antigens through the expression of innate receptors, such as toll-like receptors (TLRs). Next, DCs process fragments of these antigens for T lymphocytes, which causes an effector immune response. Dendritic cells also express a number of co-stimulatory molecules and secrete soluble mediators. The nature of the lymphocyte response (Th1 or Th2) largely depends on the quantity of peptides, co-stimulatory molecules and cytokines that DCs present to T lymphocytes [9, 19, 20].

The SPM influences antigen-presenting cells and increases antigen immunogenicity. Numerous studies have shown that stimulation of SPM accelerates maturation of DCs, as well as increases CD80+ expression and proinflammatory cytokine release [9, 21, 22]. Active maturation of DCs triggers the T lymphocyte response and enhances cytokine production by T-cells [21, 23]. Under the impact of SPM, DCs trigger CD4+ and CD8+ cell responses characterized by increased production of IFN-γ and IL-17A [9, 22]. Furthermore, amount of natural killer cells in peripheral blood decreases [11, 25]. B lymphocytes also represent an important link in forming the immune response to SPM exposure. There are data showing the relationship between the action of SPM and a decrease in the production of immunoglobulin (Ig)A and an increase in the levels of IgM, IgG and IgE [9, 26-28].

Alveolar macrophages (AMs) are the major immune cell population of the airways. One of their main functions is the phagocytosis of SPM and certain types of microorganisms in the lungs, which is the initial stage of their removal. AMs are also capable of phagocytosing carbon-containing particles [9, 29, 30]. When exposed to SPM, AMs experience a decrease in motility and mucociliary clearance, which leads to the development of ROS-mediated oxidative stress, especially during chronic inhalation of microparticles [9, 31]. Exposure to SPM may induce a Th2-type immune response and reduce the phagocytic ability of AMs, which may be associated with TLR2 and TLR4 [11]. SPM can stimulate the production of proinflammatory cytokines by macrophages [9, 14, 31]. Cytokines, especially TNF-α and IL-1β produced by macrophages, can also stimulate epithelial cells and trigger an enhanced response to microtoxicants.

Exposure to SPM leads to a significant increase in the numbers of neutrophils and eosinophils [32]. Eosinophils are effector cells that secrete cytokines involved in the activation of Th2-type T helper cells. Currently, the effect of SPM on eosinophilic inflammation is poorly studied [9]. However, there is evidence that in patients with respiratory diseases, oxidative stress induced by SPM can cause eosinophilic airway inflammation, enhance atopic allergic sensitization and increase susceptibility to infections [33, 34]. Neutrophils are particularly important granulocytes when considering the effects of SPM on the body, as they are the most abundant leukocyte cells in the blood and are rapidly transported to sites of inflammation. Published studies confirmed that when exposed to microtoxicants, neutrophils infiltrate into the bronchial mucosa activating and increasing the production of IL-8 [35]. At the same time, neutrophils express the enzymes NADPH oxidase and myeloperoxidase, which produce superoxide anions and hypochlorite anions [36].


The role of oxidative stress induced by SPM in the formation of the immune response

SPM can penetrate not only into the respiratory tract and lungs, but also into the circulatory system. The main mechanism of this action is the induction of oxidative stress in cells. Mechanisms of oxidative stress may involve the formation of oxidants on the surface of SPM, the release of metals or organic components from particles and the initiation of an inflammatory response. Activation of epithelial cells and resident macrophages, recruitment and activation of neutrophils, eosinophils, monocytes and lymphocytes are also mechanisms of response to the effects of SPM [37]. SPMs are known to stimulate cells to produce proinflammatory cytokines and chemokines. The ability of T-cells to produce a specific set of cytokines and differentiate T-cells is programmed by transcription factors. E.g., the main factors for Th1 and Th2 are T-bet and Runx3, and GATA3, respectively. SPM causes airway inflammation by regulating the expression of transcription factors. Exposure to SPM has been shown to disrupt the balance between Th1/Th2 cells, with a decrease in the percentage of Th1 cells due to the suppression of Runx3 and an increase in the number of Th2 cells due to the activation of GATA3 expression [33, 38, 39]. Therefore, exposure to SPM can trigger a cascade of immune dysfunction, which can lead to the development or progression of SPM-related pathologies [8, 9].

Oxidative stress products trigger the mitogen-activated protein kinase (MAPK) signaling cascade that leads to the activation of the redox-sensitive transcription factor (NF-κB), which regulates the expression of many proinflammatory genes, including cytokine genes and their receptors (Figure 2) [40]. Moreover, SPM is capable of generating reactive oxygen species (ROS), promoting oxidative stress and reducing the level of endogenous antioxidants. Organic compounds present in SPM can donate electrons to O2 molecules to form superoxide free radicals. SPM metals similarly donate electrons to form superoxide and hydrogen peroxide and can directly deplete endogenous thiol antioxidants [8, 9, 41, 42]. Oxidative stress stimulates the generation of intracellular signals that can induce inflammatory reactions, including the production of interleukins [9]. Exposure to microtoxicants leads to the synthesis of IL-1β, IL-6 and tumor necrosis factor (TNF-α) by T lymphocytes. Activation of this pathway also determines the production of C-reactive protein and serum amyloid A [7, 32, 43, 44]. In addition to activating proinflammatory pathways, ROS can cause damage to cellular proteins. The inflammatory response to airborne microtoxicants is also driven by mechanisms of alteration and damage to both microRNA and DNA, which may involve various genes and processes [45].


Figure 2. Mechanisms of immune response during exposure to SPM.


The development of oxidative stress and ROS production leads to mitochondrial damage, which is characterized by three key processes: damage to mitochondrial DNA (mtDNA), protein oxidation and activation of lipid peroxidation processes. SPM can cause a decrease in mitochondrial membrane potential and activate mitochondria-mediated apoptosis [8, 46-49]. MtDNA and ROS are involved in the transcriptional regulation of immune cells. During the development of SPM-mediated mitochondrial dysfunction, molecular patterns associated with damage are released into the cytoplasm and detected by pattern recognition receptors, which triggers the formation of an immune response. Signaling mechanisms are generated in immune cells leading to the activation of NF-κB, MAPK and interferon regulatory factor, which control the expression of proinflammatory chemokines and cytokines [8, 50-52].

The maintenance of thiol-disulfide homeostasis ensured by the activity of the thioredoxin and glutathione systems, plays a significant role in the regulation of the redox balance in cells and in protecting the body from oxidative stress. Reversible post-translational disulfide modifications of proteins and their subsequent reduction by thiol-disulfide-dependent antioxidant enzymes constitute the most significant mechanism of intracellular redox signaling. The thioredoxin system plays an important role in immune responses and regulation of inflammation. Under stress conditions, thioredoxin protects immune cells from oxidative stress and apoptosis. The thioredoxin system ensures the restoration of disulfide bonds in proteins damaged by oxidation. Another example of redox regulation is the activation of the transcription factor NF-κB by cytosolic thioredoxin, which regulates the immune response, apoptosis and the cell cycle [53-57].

The glutathione system maintains a reduced intracellular environment ensuring the formation of the correct tertiary structure of proteins and regulating key intracellular processes, including the activity of the thioredoxin system. As an antioxidant, glutathione directly neutralizes ROS generated by atmospheric SPM and inhibits lipid peroxidation. It is involved in the detoxification of hydrogen peroxide by various glutathione peroxidases, helping to protect cell membranes from oxidative stress. Glutathione activates a number of signaling pathways, including those associated with the transcription factor NF-κB and MAPKs [53-56].


Immune response mechanisms during exposure to SPM

Stimulation of cells by SPM involves a variety of mechanisms including TLRs, ROS, and polycyclic aromatic hydrocarbon (PAH) pathways, such as the aryl hydrocarbon receptor. These, in turn, activate proinflammatory intracellular signaling cascades, such as nuclear factor (NF-κB) and MAPK pathways [9, 58].

Production of ROS by SPM and formation of oxidative stress induce transmission of NF-κB and MAPK signals. Although both signaling pathways are activated upon exposure to SPM, the NF-κB pathway has been found to play a crucial role [57, 59-62]. Active oxygen species can directly affect cellular calcium channels, thereby disrupting the transmission of intracellular ionic signals. Intracellular Ca2+ is an important signaling system that can affect the NF-κB pathway [9, 63]. Lung oxidant/antioxidant imbalance also leads to NF-κB activation [62]. SPM induces nuclear translocation of NF-κB and production of inflammatory cytokines in human bronchial epithelial cells [61, 64].

TLRs play a significant role in the activation of inflammatory pathways mediated by exposure to SPM [32, 61, 65]. A dose-dependent increase in TLR2, TLR4, and MyD88 levels occurs under the impact of microtoxicants, leading to the development of systemic inflammation [32, 66-71]. TLR4 also activates the TIR base containing adaptor-inducing interferon-β (TRIF) located on the endosome [70]. There is evidence that upon exposure to SPM, activation of TLR4 triggers a signal transduction cascade and activates NF-κB phosphorylation, which leads to increased expression of proinflammatory cytokines, such as TNF-α, IL-6 and IL-1β [72]. Thus, TLR2 and TLR4 play a key role in the development of the inflammatory process when exposed to SPM. Once a TLR binds to a ligand, molecular adapters, including MyD88, trigger a cascade of signaling reactions [32, 61, 73].

SPM influences the release of proinflammatory cytokines, which is regulated by aryl hydrocarbon receptor (AHR) signaling [9, 74, 75]. In addition to the activation of transcription enzymes, AHRs are associated with the differentiation of Th17 lymphocytes [76, 77]. AHR is expressed in various T-cells: maximally in Th17 cells and minimally in naïve Th0 cells [77]. AHR is critical for the balance of TReg7 and Th17 cells. The degree and duration of AHR activation changes the balance between these effector and regulatory responses. Th17 cells produce IL-17 responsible for the development of inflammation when exposed to AHR [77-79].

Important participants in the cytokine regulation under the influence of SPM are IL-4 and IL-6. It has been shown that both short-term and long-term exposures to SPM lead to a dose-dependent increase in IL-6 production [14, 53, 80-82]. Under the influence of SPM, the increase in IL-6 expression is regulated by the TLR2 and TLR4/NADPH oxidase/ROS/NF-κB signaling pathways. We emphasize that activation of the NF-κB pathway is the key process initiating the cascade of reactions [54, 67, 68]. There is evidence that in patients with COPD, SPM of micro-sized fractions contributes to the modulation of the IL-6 signaling pathway in the direction of conventional signal transduction to T helper blood cells to regulate the inflammatory process and compensate for apoptotic changes [53]. Exposure to air microtoxicants also leads to a significant increase in IL-4 levels [83]. An experimental study on mice showed an increase in IL-4 production in response to exposure to SPM in bronchial asthma [84]. Another study showed that as COPD worsened under conditions of high anthropogenic load, circulating T helper cells experienced a decrease in the expression of IL-4R and an increase in the synthesis of IL-6R, thereby indicating inhibition of the anti-inflammatory activity of IL-4 and activation of the anti-inflammatory and anti-apoptotic effects of IL-6 on these cells [53].


Effect of qualitative SPM composition on the immune response

The formation of the response is influenced by various components of SPM, including adsorbed metals, and organic substances such as PAHs (benzo[α]pyrene, benzo[β]fluoranthene, pyrene), PAH-like compounds, quinolines, etc., which may cause oxidative stress.

Binding of PAH ligand triggers nuclear translocation and induction of xenobiotic metabolic enzymes, such as cytochrome P450 genes (CYP1A1, CYP1B1, CYP5), which in turn produce more cytotoxic and genotoxic products [65]. When exposed to PAHs, inflammasome activation occurs through the aryl hydrocarbon receptor pathway. Cells have a specific mechanism (AHR) for the perception of PAHs that is a cytosolic receptor sensitive to environmental factors [9, 77, 85].

Metals adsorbed on SPM, when interacting with enzymes expressed by neutrophils (NADPH oxidase, myeloperoxidase), are capable of catalyzing a further redox cycle and causing oxidative damage [9]. There is evidence that heavy metal-rich SPM can stimulate Th2 and Th17 inflammation, which is accompanied by airway hyperresponsiveness and the release of cytokines (IL-5, IL-13, IFN-γ and IL-17A) [86].

SPM may contain lipopolysaccharides (LPS) and fungal spores, which are natural ligands of TLRs, as well as oxidized phospholipids and nucleic acids that act as alternative TLR agonists [9, 19]. LPS stimulate cells through TLR4; however, LPS can also stimulate airway epithelial cells through TLR2 [9, 65, 87]. Moreover, the ratio of these two pathways varies depending on different cell types and size ranges, as well as on the qualitative composition of SPM [9, 65]. Hence, studying the composition of SPM in different regions is a key issue in examining the impact of airborne SPM on human health.



Hence, immunological responses associated with exposure to SPM are considered to be the result of a synergistic effect of systemic and local inflammation. Under the influence of SPM, a complex of cellular and molecular processes is triggered, causing the launch of specific signaling pathways that determine the outcome of the formation of environmentally dependent pathology. Despite the available evidence, some response mechanisms remain poorly understood. The immune response may depend on the qualitative, quantitative and dimensional nature of the microtoxicants, the physiological state of the body and the duration of exposure. Therefore, studying the parameters of the SPM of specific zones, their impact on the human body, and identifying subtle cellular mechanisms can help in the development of new strategies for the prevention of environmentally dependent pathologies.


Conflict of interest

The authors declare no conflicts of interest.

  1. WHO global air quality guidelines. Particulate matter (PM2.5 and PM10), ozone, nitrogen dioxide, sulfur dioxide and carbon monoxide. Geneva: World Health Organization. 2021; 290 p. https://www.who.int/publications/i/item/9789240034228.
  2. Kim KH, Kabir E, Kabir S. A review on the human health impact of airborne particulate matter. Environ Int 2015; 74: 136-143. https://doi.org/10.1016/j.envint.2014.10.005.
  3. Thompson JE. Airborne particulate matter: Human exposure and health effects. J Occup Environ Med 2018; 60(5): 392-423. https://doi.org/10.1097/JOM.0000000000001277.
  4. Puett RC, Yanosky JD, Mittleman MA, Montresor-Lopez J, Bell RA, Crume TL, et al. Inflammation and acute traffic-related air pollution exposures among a cohort of youth with type 1 diabetes. Environ Int 2019; 132: 105064. https://doi.org/10.1016/j.envint.2019.105064.
  5. Marrot L. Pollution and sun exposure: A deleterious synergy. Mechanisms and opportunities for skin protection. Curr Med Chem 2018; 25(40): 5469-5486. https://doi.org/10.2174/0929867324666170918123907.
  6. Hahad O, Lelieveld J, Birklein F, Lieb K, Daiber A, Munzel T. Ambient air pollution increases the risk of cerebrovascular and neuropsychiatric disorders through induction of inflammation and oxidative stress. Int J Mol Sci 2020; 21(12): 4306. https://doi.org/10.3390/ijms21124306.
  7. Franza L, Cianci R. Pollution, inflammation, and vaccines: A complex crosstalk. Int J Environ Res Public Health 2021; 18(12): 6330. https://doi.org/10.3390/ijerph18126330.
  8. Kondratyeva EV, Vitkina TI. Effect of atmospheric particulate matter on the functional state of mitochondria. Russ Open Med J 2023; 12: e0106. https://doi.org/10.15275/rusomj.2023.0106.
  9. Glencross DA, Ho TR, Camina N, Hawrylowicz CM, Pfeffer PE. Air pollution and its effects on the immune system. Free Radic Biol Med 2020; 151: 56-68. https://doi.org/10.1016/j.freeradbiomed.2020.01.179.
  10. Chen T, Chen F, Wang K, Ma X, Wei X, Wang W, et al. Acute respiratory response to individual particle exposure (PM1.0, PM2.5 and PM10) in the elderly with and without chronic respiratory diseases. Environ Pollut 2021; 271: 116329. https://doi.org/10.1016/j.envpol.2020.116329.
  11. Yang L, Li C, Tang X. The impact of PM2.5 on the host defense of respiratory system. Front Cell Dev Biol 2020; 8: 91. https://doi.org/10.3389/fcell.2020.00091.
  12. Marin-Palma D, Fernandez GJ, Ruiz-Saenz J, Taborda NA, Rugeles MT, Hernandez JC. Particulate matter impairs immune system function by up-regulating inflammatory pathways and decreasing pathogen response gene expression. Sci Rep 2023; 13(1): 12773. https://doi.org/10.1038/s41598-023-39921-w.
  13. Honda A, Fukushima W, Oishi M, Tsuji K, Sawahara T, Hayashi T, et al. Effects of components of PM2.5 collected in Japan on the respiratory and immune systems. Int J Toxicol 2017; 36(2): 153-164. https://doi.org/10.1177/1091581816682224.
  14. Mitschik S, Schierl R, Nowak D, Jörres RA. Effects of particulate matter on cytokine production in vitro: A comparative analysis of published studies. Inhal Toxicol 2008; 20(4): 399-414. https://doi.org/10.1080/08958370801903784.
  15. Kido T, Tamagawa E, Bai N, Suda K, Yang HH, Li Y, et al. Particulate matter induces translocation of IL-6 from the lung to the systemic circulation. Am J Respir Cell Mol Biol 2011; 44(2): 197-204. https://doi.org/10.1165/rcmb.2009-0427OC.
  16. Thompson AM, Zanobetti A, Silverman F, Schwartz J, Coull B, Urch B, et al. Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen. Environ Health Perspect 2010; 118(1): 120-124. https://doi.org/10.1289/ehp.0900550.
  17. Becher B, Tugues S, Greter M. GM-CSF: From growth factor to central mediator of tissue inflammation. Immunity 2016; 45(5): 963-973. https://doi.org/10.1016/j.immuni.2016.10.026.
  18. Wei T, Tang M. Biological effects of airborne fine particulate matter (PM2.5) exposure on pulmonary immune system. Environ Toxicol Pharmacol 2018; 60: 195-201. https://doi.org/10.1016/j.etap.2018.04.004.
  19. Ren Y, Ichinose T, He M, Youshida S, Nishikawa M, Sun G. Co-exposure to lipopolysaccharide and desert dust causes exacerbation of ovalbumin-induced allergic lung inflammation in mice via TLR4/MyD88-dependent and -independent pathways. Allergy Asthma Clin Immunol 2019; 15: 82. https://doi.org/10.1186/s13223-019-0396-4.
  20. Paplinska-Goryca M, Misiukiewicz-Stepien P, Proboszcz M, Nejman-Gryz P, Gorska K, Zajusz-Zubek E, et al. Interactions of nasal epithelium with macrophages and dendritic cells variously alter urban PM-induced inflammation in healthy, asthma and COPD. Sci Rep 2021; 11(1): 13259. https://doi.org/10.1038/s41598-021-92626-w.
  21. Porter M, Karp M, Killedar S, Bauer SM, Guo J, Williams D, et al. Diesel-enriched particulate matter functionally activates human dendritic cells. Am J Respir Cell Mol Biol 2007; 37(6): 706-719. https://doi.org/10.1165/rcmb.2007-0199OC.
  22. Matthews NC, Faith A, Pfeffer P, Lu H, Kelly FJ, Hawrylowicz CM, et al. Urban particulate matter suppresses priming of T helper type 1 cells by granulocyte/macrophage colony-stimulating factor-activated human dendritic cells. Am J Respir Cell Mol Biol 2014; 50(2): 281-291. https://doi.org/10.1165/rcmb.2012-0465OC.
  23. Matthews NC, Pfeffer PE, Mann EH, Kelly FJ, Corrigan CJ, Hawrylowicz CM, et al. Urban particulate matter-activated human dendritic cells induce the expansion of potent inflammatory Th1, Th2, and Th17 effector cells. Am J Respir Cell Mol Biol 2016; 54(2): 250-262. https://doi.org/10.1165/rcmb.2015-0084OC.
  24. Bleck B, Tse DB, Jaspers I, Curotto de Lafaille MA, Reibman J. Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation. J Immunol 2006; 176(12): 7431-7437. https://doi.org/10.4049/jimmunol.176.12.7431.
  25. Dolgikh OV, Dianova DG, Nikonoshina NA. Innate and adaptive immunity in workers of the main occupations exposed to fine particulate matter in potassium chloride production. Public Health and Life Environment 2022; (4): 63-69. Russian. https://doi.org/10.35627/2219-5238/2022-30-4-63-69.
  26. Zhao J, Gao Z, Tian Z, Xie Y, Xin F, Jiang R, et al. The biological effects of individual-level PM(2.5) exposure on systemic immunity and inflammatory response in traffic policemen. Occup Environ Med 2013; 70(6): 426-431. https://doi.org/10.1136/oemed-2012-100864.
  27. Castaneda AR, Vogel CFA, Bein KJ, Hughes HK, Smiley-Jewell S, Pinkerton KE. Ambient particulate matter enhances the pulmonary allergic immune response to house dust mite in a BALB/c mouse model by augmenting Th2- and Th17-immune responses. Physiol Rep 2018; 6(18): e13827. https://doi.org/10.14814/phy2.13827.
  28. Wang Y, Tang N, Mao M, Zhou Y, Wu Y, Li J, et al. Fine particulate matter (PM2.5) promotes IgE-mediated mast cell activation through ROS/Gadd45b/JNK axis. J Dermatol Sci 2021; 102(1): 47-57. https://doi.org/10.1016/j.jdermsci.2021.02.004.
  29. Terashima T, Wiggs B, English D, Hogg JC, van Eeden SF. Phagocytosis of small carbon particles (PM10) by alveolar macrophages stimulates the release of polymorphonuclear leukocytes from bone marrow. Am J Respir Crit Care Med 1997; 155(4): 1441-1447. https://doi.org/10.1164/ajrccm.155.4.9105091.
  30. Bai Y, Brugha RE, Jacobs L, Grigg J, Nawrot TS, Nemery B. Carbon loading in airway macrophages as a biomarker for individual exposure to particulate matter air pollution – A critical review. Environ Int 2015; 74: 32-41. https://doi.org/10.1016/j.envint.2014.09.010.
  31. Barskova LS, Vitkina TI, Gvozdenko TA, Kondratyeva EV, Veremchuk LV. Mechanism of response of alveolar macrophages in wistar rats to the composition of atmospheric suspensions. Atmosphere 2022; 13(9): 1500. https://doi.org/10.3390/atmos13091500.
  32. Le Y, Hu X, Zhu J, Wang C, Yang Z, Lu D. Ambient fine particulate matter induces inflammatory responses of vascular endothelial cells through activating TLR-mediated pathway. Toxicol Ind Health 2019; 35(10): 670-678. https://doi.org/10.1177/0748233719871778.
  33. Huang KL, Liu SY, Chou CC, Lee YH, Cheng TJ. The effect of size-segregated ambient particulate matter on Th1/Th2-like immune responses in mice. PLoS One 2017; 12(2): e0173158. https://doi.org/10.1371/journal.pone.0173158.
  34. Rouadi PW, Idriss SA, Naclerio RM, Peden DB, Ansotegui IJ, Canonica GW, et al. Immunopathological features of air pollution and its impact on inflammatory airway diseases (IAD). World Allergy Organ J 2020; 13(10): 100467. https://doi.org/10.1016/j.waojou.2020.100467.
  35. McCreanor J, Cullinan P, Nieuwenhuijsen MJ, Stewart-Evans J, Malliarou E, Jarup L, et al. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med 2007; 357(23): 2348-2358. https://doi.org/10.1056/NEJMoa071535.
  36. Robinson JM. Phagocytic leukocytes and reactive oxygen species. Histochem Cell Biol 2009; 131(4): 465-469. https://doi.org/10.1007/s00418-009-0565-5.
  37. Valacchi G, Magnani N, Woodby B, Ferreira SM, Evelson P. Particulate matter induces tissue oxinflammation: From mechanism to damage. Antioxid Redox Signal 2020; 33(4): 308-326. https://doi.org/10.1089/ars.2019.8015.
  38. Pang L, Yu P, Liu X, Fan Y, Shi Y, Zou S. Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice. Mol Med Rep 2021; 23(5): 378. https://doi.org/10.3892/mmr.2021.12017.
  39. Lu X, Li R, Yan X. Airway hyperresponsiveness development and the toxicity of PM2.5. Environ Sci Pollut Res Int 2021; 28(6): 6374-6391. https://doi.org/10.1007/s11356-020-12051-w.
  40. Wang J, Huang J, Wang L, Chen C, Yang D, Jin M, et al. Urban particulate matter triggers lung inflammation via the ROS-MAPK-NF-κB signaling pathway. J Thorac Dis 2017; 9(11): 4398-4412. https://doi.org/10.21037/jtd.2017.09.135.
  41. Ghio AJ, Carraway MS, Madden MC. Composition of air pollution particles and oxidative stress in cells, tissues, and living systems. J Toxicol Environ Health B Crit Rev 2012; 15(1): 1-21. https://doi.org/10.1080/10937404.2012.632359.
  42. Golokhvast K, Vitkina T, Gvozdenko T, Kolosov V, Yankova V, Kondratieva E, et al. Impact of atmospheric microparticles on the development of oxidative stress in healthy city/industrial seaport residents. Oxid Med Cell Longev 2015; 2015: 412173. https://doi.org/10.1155/2015/412173.
  43. Moller P, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Klingberg H, et al. Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutat Res Rev Mutat Res 2014; 762: 133-166. https://doi.org/10.1016/j.mrrev.2014.09.001.
  44. Niu X, Wang Y, Ho SSH, Chuang HC, Sun J, Qu L, et al. Characterization of organic aerosols in PM1 and their cytotoxicity in an urban roadside area in Hong Kong. Chemosphere 2021; 263: 128239. https://doi.org/10.1016/j.chemosphere.2020.128239.
  45. Alves NDO, Pereira GM, Di Domenico M, Costanzo G, Benevenuto S, de Oliveira Fonoff AM, et al. Inflammation response, oxidative stress and DNA damage caused by urban air pollution exposure increase in the lack of DNA repair XPC protein. Environ Int 2020; 145: 106150. https://doi.org/10.1016/j.envint.2020.106150.
  46. Fetterman JL, Sammy MJ, Ballinger SW. Mitochondrial toxicity of tobacco smoke and air pollution. Toxicology 2017; 391: 18-33. https://doi.org/10.1016/j.tox.2017.08.002.
  47. Zheng L, Liu S, Zhuang G, Xu J, Liu Q, Zhang X, et al. Signal transductions of BEAS-2B cells in response to carcinogenic PM2.5 exposure based on a microfluidic system. Anal Chem 2017; 89(10): 5413-5421. https://doi.org/10.1021/acs.analchem.7b00218.
  48. Jin X, Xue B, Zhou Q, Su R, Li Z. Mitochondrial damage mediated by ROS incurs bronchial epithelial cell apoptosis upon ambient PM2.5 exposure. J Toxicol Sci 2018; 43(2): 101-111. https://doi.org/10.2131/jts.43.101.
  49. Denisenko YuK, Novgorodtseva ТP, Vitkina TI, Zhukova NV, Gvozdenko ТА, Knyshova VV. The response of platelet and leukocyte mitochondria of healthy residents on the impact of atmospheric microparticles. Russian Journal of Physiology 2019; 105(1): 111-120. Russian. https://doi.org/10.1134/S0869813919010023.
  50. Pardo M, Qiu X, Zimmermann R, Rudich Y. Particulate matter toxicity is Nrf2 and mitochondria dependent: The roles of metals and polycyclic aromatic hydrocarbons. Chem Res Toxicol 2020; 33(5): 1110-1120. https://doi.org/10.1021/acs.chemrestox.0c00007.
  51. Pardo M, Xu F, Shemesh M, Qiu X, Barak Y, Zhu T, et al. Nrf2 protects against diverse PM2.5 components-induced mitochondrial oxidative damage in lung cells. Sci Total Environ 2019; 669: 303-313. https://doi.org/10.1016/j.scitotenv.2019.01.436.
  52. Sharma J, Parsai K, Raghuwanshi P, Ali SA, Tiwari V, Bhargava A, et al. Emerging role of mitochondria in airborne particulate matter-induced immunotoxicity. Environ Pollut 2021; 270: 116242. https://doi.org/10.1016/j.envpol.2020.116242.
  53. Vitkina TI, Barskova LS, Zyumchenko NE, Tokmakova NP, Gvozdenko TA, Golokhvast KS. Balance of glutathione-related processes in alveolar macrophages under exposure to suspended particulate matter of atmospheric air in of wistar rats. Hygiene and Sanitation 2020; 99(2): 200-205. Russian. https://doi.org/10.47470/0016-9900-2020-99-2-200-205.
  54. Vitkina TI, Gvozdenko TA, Rakitskiy VN, Kolosov VP, Yankova VI, Gorkavaya Ayu, et al. On the role of the thioldisulphyde system in protection the human body from aerosol air pollution. Hygiene and Sanitation 2017; 96(8): 701-706. Russian. https://doi.org/10.47470/0016-9900-2017-96-8-701-706.
  55. Vitkina TI, Sidletskaya KA. Diagnostic criteria for the progression of the chronic obstructive pulmonary disease under a high technogenic load. Hygiene and Sanitation 2020; 99(2): 140-144. Russian. https://doi.org/10.47470/0016-9900-2020-99-2-140-144.
  56. Barskova LS, Vitkina TI. Regulation by thiol disulfide and antioxidant systems of oxidative stress induced by atmospheric suspended particles. Bulletin of Physiology and Pathology of Respiration 2019; (73): 112-124. Russian. https://doi.org/10.36604/1998-5029-2019-73-112-124.
  57. Barskova LS, Vitkina TI, Veremchuk LV, Gvozdenko TA. Assessment of the influence of the composition of atmospheric microparticles on redox homeostasis of alveolar macrophages. Hygiene and Sanitation 2022; 101(9): 1004-1010. Russian. https://doi.org/10.47470/0016-9900-2022-101-9-1004-1010.
  58. Muralidharan S, Mandrekar P. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol 2013; 94(6): 1167-1184. https://doi.org/10.1189/jlb.0313153.
  59. Liu J, Li S, Fei X, Nan X, Shen Y, Xiu H, et al. Increased alveolar epithelial TRAF6 via autophagy-dependent TRIM37 degradation mediates particulate matter-induced lung metastasis. Autophagy 2022; 18(5): 971-989. https://doi.org/10.1080/15548627.2021.1965421.
  60. Wan F, Lenardo MJ. The nuclear signaling of NF-kappaB: Current knowledge, new insights, and future perspectives. Cell Res 2010; 20(1): 24-33. https://doi.org/10.1038/cr.2009.137.
  61. Song Y, Ichinose T, Morita K, Yoshida Y. The toll like receptor 4-myeloid differentiation factor 88 pathway is essential for particulate matter-induced activation of CD4-positive cells. J Appl Toxicol 2019; 39(2): 354-364. https://doi.org/10.1002/jat.3726.
  62. Piao CH, Fan Y, Nguyen TV, Shin HS, Kim HT, Song CH, et al. PM2.5 exacerbates oxidative stress and inflammatory response through the Nrf2/NF-κB signaling pathway in OVA-induced allergic rhinitis mouse model. Int J Mol Sci 2021; 22(15): 8173. https://doi.org/10.3390/ijms22158173.
  63. Fernando IPS, Jayawardena TU, Kim HS, Lee WW, Vaas APJP, De Silva HIC, et al. Beijing urban particulate matter-induced injury and inflammation in human lung epithelial cells and the protective effects of fucosterol from Sargassum binderi (Sonder ex J. Agardh). Environ Res 2019; 172: 150-158. https://doi.org/10.1016/j.envres.2019.02.016.
  64. Longhin E, Capasso L, Battaglia C, Proverbio MC, Cosentino C, Cifola I, et al. Integrative transcriptomic and protein analysis of human bronchial BEAS-2B exposed to seasonal urban particulate matter. Environ Pollut 2016; 209: 87-98. https://doi.org/10.1016/j.envpol.2015.11.013.
  65. Shoenfelt J, Mitkus RJ, Zeisler R, Spatz RO, Powell J, Fenton MJ, et al. Involvement of TLR2 and TLR4 in inflammatory immune responses induced by fine and coarse ambient air particulate matter. J Leukoc Biol 2009; 86(2): 303-312. https://doi.org/10.1189/jlb.1008587.
  66. Noreen M, Arshad M. Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility. Immunol Res 2015; 62(2): 234-252. https://doi.org/10.1007/s12026-015-8640-6.
  67. Vo TTT, Wee Y, Chen YL, Cheng HC, Tuan VP, Lee IT. Surfactin attenuates particulate matter-induced COX-2-dependent PGE2 production in human gingival fibroblasts by inhibiting TLR2 and TLR4/MyD88/NADPH oxidase/ROS/PI3K/Akt/NF-κB signaling pathway. J Periodontal Res 2021; 56(6): 1185-1199. https://doi.org/10.1111/jre.12932.
  68. Vo TTT, Hsu CY, Wee Y, Chen YL, Cheng HC, Wu CZ, et al. Carbon monoxide-releasing molecule-2 ameliorates particulate matter-induced aorta inflammation via toll-like receptor/NADPH oxidase/ROS/NF-κB/IL-6 inhibition. Oxid Med Cell Longev 2021; 2021: 2855042. https://doi.org/10.1155/2021/2855042.
  69. Wang J, Xue R, Li C, Hu L, Li Q, Sun Y, et al. Inhalation of subway fine particles induces murine extrapulmonary organs damage. Sci Total Environ 2023; 878: 163181. https://doi.org/10.1016/j.scitotenv.2023.163181.
  70. Volkov MYu. Role of Toll-like receptors and their endogenous ligands in the pathogenesis of rheumatoid arthritis: a review of literature. Rheumatology Science and Practice 2016; 54(1): 78-85. Russian. https://doi.org/10.14412/1995-4484-2016-78-85.
  71. Sidletskaya KA, Vitkina TI, Denisenko YK, Mineeva EE. Role of toll-like receptor 2 in regulation of T-helper immune response in chronic obstructive pulmonary disease. Can Respir J 2021; 2021: 5596095. https://doi.org/10.1155/2021/5596095.
  72. Han B, Li X, Ai RS, Deng SY, Ye ZQ, Deng X, et al. Atmospheric particulate matter aggravates cns demyelination through involvement of TLR-4/NF-kB signaling and microglial activation. Elife 2022; 11: e72247. https://doi.org/10.7554/eLife.72247.
  73. Satoh T, Akira S. Toll-like receptor signaling and its inducible proteins. Microbiol Spectr 2016; 4(6). https://doi.org/10.1128/microbiolspec.MCHD-0040-2016.
  74. den Hartigh LJ, Lame MW, Ham W, Kleeman MJ, Tablin F, Wilson DW. Endotoxin and polycyclic aromatic hydrocarbons in ambient fine particulate matter from Fresno, California initiate human monocyte inflammatory responses mediated by reactive oxygen species. Toxicol In Vitro 2010; 24(7): 1993-2002. https://doi.org/10.1016/j.tiv.2010.08.017.
  75. Marris CR, Kompella SN, Miller MR, Incardona JP, Brette F, Hancox JC, et al. Polyaromatic hydrocarbons in pollution: A heart-breaking matter. J Physiol 2020; 598(2): 227-247. https://doi.org/10.1113/JP278885.
  76. Suzuki T, Hidaka T, Kumagai Y, Yamamoto M. Environmental pollutants and the immune response. Nat Immunol 2020; 21(12): 1486-1495. https://doi.org/10.1038/s41590-020-0802-6.
  77. O’Driscoll CA, Gallo ME, Fechner JH, Schauer JJ, Mezrich JD. Real-world PM extracts differentially enhance Th17 differentiation and activate the aryl hydrocarbon receptor (AHR). Toxicology 2019; 414: 14-26. https://doi.org/10.1016/j.tox.2019.01.002.
  78. Ehrlich AK, Pennington JM, Bisson WH, Kolluri SK, Kerkvliet NI. TCDD, FICZ, and Other High Affinity AhR ligands dose-dependently determine the fate of CD4+ T cell differentiation. Toxicol Sci 2018; 161(2): 310-320. https://doi.org/10.1093/toxsci/kfx215.
  79. Zhou X, Dai H, Jiang H, Rui H, Liu W, Dong Z, et al. Corrigendum: MicroRNAs: Potential mediators between particulate matter 2.5 and Th17/Treg immune disorder in primary membranous nephropathy. Front Pharmacol 2023; 14: 1166591. https://doi.org/10.3389/fphar.2023.1166591.
  80. Klümper C, Krämer U, Lehmann I, von Berg A, Berdel D, Herberth G, et al. Air pollution and cytokine responsiveness in asthmatic and non-asthmatic children. Environ Res 2015; 138: 381-390. https://doi.org/10.1016/j.envres.2015.02.034.
  81. Tsai DH, Amyai N, Marques-Vidal P, Wang JL, Riediker M, Mooser V, et al. Effects of particulate matter on inflammatory markers in the general adult population. Part Fibre Toxicol 2012; 9: 24. https://doi.org/10.1186/1743-8977-9-24.
  82. Liu CW, Lee TL, Chen YC, Liang CJ, Wang SH, Lue JH, et al. PM2.5-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway. Part Fibre Toxicol 2018; 15(1): 4. https://doi.org/10.1186/s12989-018-0240-x.
  83. Zhou J, Geng F, Xu J, Peng L, Ye X, Yang D, et al. PM2.5 exposure and cold stress exacerbates asthma in mice by increasing histone acetylation in IL-4 gene promoter in CD4+ T cells. Toxicol Lett 2019; 316: 147-153. https://doi.org/10.1016/j.toxlet.2019.09.011.
  84. Zhang X, Zhong W, Meng Q, Lin Q, Fang C, Huang X, et al. Ambient PM2.5 exposure exacerbates severity of allergic asthma in previously sensitized mice. J Asthma 2015; 52(8): 785-794. https://doi.org/10.3109/02770903.2015.1036437.
  85. Ho CC, Wu WT, Lin YJ, Weng CY, Tsai MH, Tsai HT, et al. Aryl hydrocarbon receptor activation-mediated vascular toxicity of ambient fine particulate matter: contribution of polycyclic aromatic hydrocarbons and osteopontin as a biomarker. Part Fibre Toxicol 2022; 19(1): 43. https://doi.org/10.1186/s12989-022-00482-x.
  86. Gour N, Sudini K, Khalil SM, Rule AM, Lees P, Gabrielson E, et al. Unique pulmonary immunotoxicological effects of urban PM are not recapitulated solely by carbon black, diesel exhaust or coal fly ash. Environ Res 2018; 161: 304-313. https://doi.org/10.1016/j.envres.2017.10.041.
  87. Becker S, Dailey L, Soukup JM, Silbajoris R, Devlin RB. TLR-2 is involved in airway epithelial cell response to air pollution particles. Toxicol Appl Pharmacol 2005; 203(1): 45-52. https://doi.org/10.1016/j.taap.2004.07.007.
About the Authors: 

Elena V. Kondratyeva – PhD, Research Scientist, Laboratory of Medical Ecology and Recreational Resources, Institute of Medical Climatology and Rehabilitative Treatment, Vladivostok Branch of the Far Eastern Scientific Center for Physiology and Pathology of Respiration, Vladivostok, Russia. https://orcid.org/0000-0002-3024-9873
Tatyana I. Vitkina – DSc, Professor RAS, Head of the Laboratory of Medical Ecology and Recreational Resources, Institute of Medical Climatology and Rehabilitative Treatment, Vladivostok Branch of the Far Eastern Scientific Center for Physiology and Pathology of Respiration, Vladivostok, Russia. http://orcid.org/0000-0002-1009-9011.

Received 25 September 2023, Revised 14 December 2023, Accepted 7 February 2024 
© 2023, Russian Open Medical Journal 
Correspondence to Elena V. Kondratyeva. E-mail: elena.v.kondratyeva@yandex.ru.


hcs777 hcs777 hcs777