Lymphocytes, Lymphokines, and Silicosis

Davis, Gerald S.; Holmes, Chris E.; Pfeiffer, L.; Hemenway, David R.

doi:10.1615/jenvironpatholtoxicoloncol.v20.isuppl.1.50

Cited by 61 publications

(64 citation statements)

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“…In experimental models of xenobiotic-induced lung fibrosis, contradictory results were generated by abrogating Th1 or Th2 effector cytokines. For instance, the absence of IFN-g or IL-4 in mice was not associated with a unequivocal modulation of lung fibrosis (62)(63)(64)(65). This may reflect the fact that another Th population, rather than Th1 and Th2, is involved in murine lung fibrosis.…”

Section: Discussionmentioning

confidence: 97%

IL-17A–Producing γδ T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis

Re¹,

Dumoutier

Couillin

et al. 2010

The Journal of Immunology

130

107

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IL-17–producing T lymphocytes play a crucial role in inflammation, but their possible implication in fibrosis remains to be explored. In this study, we examined the involvement of these cells in a mouse model of lung inflammation and fibrosis induced by silica particles. Upregulation of IL-17A was associated with the development of experimental silicosis, but this response was markedly reduced in athymic, γδ T cell-deficient or CD4+ T cell-depleted mice. In addition, γδ T lymphocytes and CD4+ T cells, but not macrophages, neutrophils, NK cells or CD8 T cells, purified from the lungs of silicotic mice markedly expressed IL-17A. Depletion of alveolar macrophages or neutralization of IL-23 reduced upregulation of IL-17A in the lung of silicotic mice. IL-17R–deficient animals (IL-17R−/−) or IL-17A Ab neutralization, but not IL-22−/− mice, developed reduced neutrophil influx and injury during the early lung response to silica. However, chronic inflammation, fibrosis, and TGF-β expression induced by silica were not attenuated in the absence of IL-17R or -22 or after IL-17A Ab blockade. In conclusion, a rapid lung recruitment of IL-17A–producing T cells, mediated by macrophage-derived IL-23, is associated with experimental silicosis in mice. Although the acute alveolitis induced by silica is IL-17A dependent, this cytokine appears dispensable for the development of the late inflammatory and fibrotic lung responses to silica.

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Section: Discussionmentioning

confidence: 97%

IL-17A–Producing γδ T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis

Re¹,

Dumoutier

Couillin

et al. 2010

The Journal of Immunology

130

107

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“…describes a cycle that could possibly ensue once the lung lymphocytes are activated. This would involve the release of IFN-γ and other mediators attracting and activating a secondary population of macrophages creating a cycle or loop of inflammation [111]. An additional study by Borges et.…”

Section: The Role Of Silica Exposure In Macrophage Immune Dysfunctionmentioning

confidence: 99%

Silica binding and toxicity in alveolar macrophages

Hamilton

Thakur

Holian

2008

Free Radical Biology and Medicine

333

242

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Inhalation of the crystalline form of silica is associated with a variety of pathologies from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science researchers looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage (AM) interacts with the inhaled silica particle and the consequences of silicainduced toxicity on the cellular level. Based on experimental results, several rationales have been developed on exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica) triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species (RNS) are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, where silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis is described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.

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“…Disbalance in the immune response regulation is suggested [8][9][10][11][12][13]. Enhanced levels of interferon-gamma (IFN-γ), IL-12p40 messenger ribonucleic acid (mRNA) and proteins have been observed in an experimental model of silicosis, suggesting that a T-helper (Th)-1 lymphocyte subpopulation might dominate in this disease.…”

Section: Introductionmentioning

confidence: 99%

Serum neopterin in workers exposed to inorganic dust containing free crystalline silicon dioxide

et al. 2009

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AbstractThe study was conducted among 92 male workers, divided into two groups depending on workplace and level of inorganic dust containing free crystalline SiO2 in the work environment, and 43 healthy workers without exposure to dust aerosols. The measured inhalable and respirable dust concentrations, as well as the concentration of free crystalline silica (FCS) in the respirable fraction were different for the two groups, but the percentage of free crystalline silica in the respirable fraction was almost identical. Significantly higher neopterin levels were found in workers exposed to dust, compared to the control group: 12.72 nmol/L and 6.32 nmol/L respectively (p<0.05). No significant difference was found between serum neopterin levels in both groups of the exposed workers. Among the groups with different length of service, a statistically higher neopterin level was evident only in the workers with length of service less than 10 years (p<0.05). The correlation analysis did not find a significant dependence of neopterin levels on the age of the studied workers or on the duration of smoking in packet years. The difference between neopterin levels in smokers and non-smokers was nonsignificant. The results obtained show that increased neopterin levels in the exposed workers are not influenced by individual features, duration and level of exposure to inorganic dust, but mostly by the presence of FCS in the respirable fraction.

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Lymphocytes, Lymphokines, and Silicosis

Cited by 61 publications

References 0 publications

IL-17A–Producing γδ T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis

IL-17A–Producing γδ T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis

Silica binding and toxicity in alveolar macrophages

Serum neopterin in workers exposed to inorganic dust containing free crystalline silicon dioxide

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