Immunoglobulin and lymphocyte responses following silica exposure in New Zealand mixed mice.
Epidemiological studies have shown strong associations between silica exposure and several autoimmune diseases, including scleroderma and systemic lupus erythematosus. We previously reported that the New Zealand mixed (NZM) mouse develops silicosis and exacerbated autoimmunity following crystalline silica exposure, including increased levels of autoantibodies, proteinuria, circulating immune complexes, pulmonary fibrosis, and glomerulonephritis. In this study, the NZM mouse was used to examine changes in immune activation following silica exposure by measuring levels of immunoglobulin, cytokines and lymphocyte populations. Levels of immunoglobulin (Ig) G1 were significantly decreased from 1124 +/- 244 microg/ml in saline exposed mice to 614 +/- 204 microg/ml in silica-exposed mice, suggesting a decrease in the Th2 response. The levels of tumor necrosis factor (TNF)-alpha were significantly increased (1.5-fold) in the bronchoalveolar lavage fluid of the silica-exposed mice as compared to the saline-exposed mice. The number of B1a B cells were significantly increased sixfold within the superficial cervical lymph nodes of silica-exposed mice as compared with saline-exposed mice. Following silica exposure, CD4+ T cells significantly increased threefold within the superficial cervical lymph nodes. During this increase in the number of CD4+ T cells, the number of CD4+CD25+ regulatory T cells was not significantly changed, altering the ratio of regulatory T cells to T helper cells from 1:5 to 1:8 following silica exposure. Therefore, the silica-induced alterations in immunoglobulin levels, increased TNF-alpha, increased B1a B cells and CD4+ T cells, with decreased regulatory T cells, may provide an environment that allows for increased autoreactivity. These studies begin to provide possible mechanisms for environmentally induced autoimmune diseases that have been reported in many epidemiological studies.
Brown
Jared M
JM
Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, 59812, USA. jaredb@selway.umt.edu
Pfau
Jean C
JC
Holian
Andrij
A
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000187:drug effects; D018893:Bronchoalveolar Lavage; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004785:Environmental Pollutants; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide