A protective role for T lymphocytes in asbestos-induced pulmonary inflammation and collagen deposition.
Several lines of evidence have suggested that specific (i.e., lymphocyte) immunity plays a role in chemical-induced pulmonary diseases, including asbestosis. To evaluate the influence of cell-mediated immunity in pulmonary inflammation and fibrosis evoked by asbestos fibers, we compared the effects of asbestos in immunodeficient mice (Balb/c nu/nu and severe combined immunodeficient [C3H-SCID]), immunologically normal mice of the same genetic background, and immunodeficient mice reconstituted with syngeneic T lymphocytes. Increases in lavaged cell numbers occurred in asbestos-treated immunodeficient mice compared with asbestos-treated immunocompetent or immunodeficient mice that received T lymphocytes. Differential analysis of the collected cells in treated mice demonstrated a predominantly neutrophilic infiltrate that correlated with increased levels of leukotriene B4 and prostaglandin E2. There were no significant differences between immunocompetent and athymic asbestos-treated mice in bronchoalveolar lavaged total protein. However, asbestos-treated SCID mice revealed a significant increase in protein content and lactate dehydrogenase activity compared with asbestos-treated normal mice, which did not occur in T lymphocyte-reconstituted SCID mice. Fibronectin levels were elevated in asbestos-exposed athymic mice when compared with air-exposed athymic mice or asbestos-exposed immunocompetent mice. Both asbestos-treated athymic and SCID mice showed a significant increase in total lung hydroxyproline when compared with asbestos-treated immunocompetent mice. Lung hydroxyproline was also reduced in asbestos-exposed SCID mice after T lymphocyte reconstitution and, conversely, increased in T cell-depleted Balb/c mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Corsini
E
E
Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triange Park, North Carolina.
Luster
M I
MI
Mahler
J
J
Craig
W A
WA
Blazka
M E
ME
Rosenthal
G J
GJ
D000818:Animals; D017632:Asbestos, Serpentine / Q000633:toxicity*; D001195:Asbestosis / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003094:Collagen / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D016513:Mice, SCID; D008969:Molecular Sequence Data; D011658:Pulmonary Fibrosis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D017632:Asbestos, Serpentine; D005353:Fibronectins; D012333:RNA, Messenger; D007975:Leukotriene B4; D007371:Interferon-gamma; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone; D006909:Hydroxyproline