Effects of cigarette smoke on immune response: chronic exposure to cigarette smoke impairs antigen-mediated signaling in T cells and depletes IP3-sensitive Ca(2+) stores.
Chronic exposure of mice and rats to cigarette smoke affects T-cell responsiveness that may account for the decreased T-cell proliferative and T-dependent antibody responses in humans and animals exposed to cigarette smoke. However, the mechanism by which cigarette smoke affects the T cell function is not clearly understood. Our laboratory has shown that chronic exposure of rats to nicotine inhibits the antibody-forming cell response, impairs the antigen-mediated signaling in T cells, and induces T cell anergy. To determine the mechanism of cigarette smoke-induced immunosuppression and to compare it with chronic nicotine exposure, rats were exposed to diluted, mainstream cigarette smoke for up to 30 months or to nicotine (1 mg/kg b.wt./24 h) via miniosmotic pumps for 4 weeks, and evaluated for immunological function in vivo and in vitro. This article presents evidence suggesting that T cells from long-term cigarette smoke-exposed rats exhibit decreased antigen-mediated proliferation and constitutive activation of protein tyrosine kinase and phospholipase C-gamma1 activities. Moreover, spleen cells from smoke-exposed and nicotine-treated animals have depleted inositol-1, 4,5-trisphosphate-sensitive Ca(2+) stores and a decreased ability to raise intracellular Ca(2+) levels in response to T cell antigen receptor ligation. These results suggest that chronic smoking causes T cell anergy by impairing the antigen receptor-mediated signal transduction pathways and depleting the inositol-1,4, 5-trisphosphate-sensitive Ca(2+) stores. Moreover, nicotine may account for or contribute to the immunosuppressive properties of cigarette smoke.
Kalra
R
R
Pathophysiology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Singh
S P
SP
Savage
S M
SM
Finch
G L
GL
Sopori
M L
ML
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects; D000941:Antigens / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D003367:Cotinine / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006304:Health Status; D007109:Immunity / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D051966:Phospholipase C gamma; D010947:Plants, Toxic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D012906:Smoke / Q000009:adverse effects*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014026:Nicotiana; D010738:Type C Phospholipases / Q000378:metabolism
D000941:Antigens; D007527:Isoenzymes; D018722:Nicotinic Agonists; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D012906:Smoke; D009538:Nicotine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D003367:Cotinine; D002118:Calcium