Abstract
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-γ1 activities. Moreover, spleen cells from smoke-exposed and nicotine-treated animals have depleted inositol-1,4,5-trisphosphate-sensitive Ca2+ stores and a decreased ability to raise intracellular Ca2+ 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 Ca2+ stores. Moreover, nicotine may account for or contribute to the immunosuppressive properties of cigarette smoke.
Footnotes
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Send reprint requests to: Mohan Sopori, Ph.D., Pathophysiology Division, Box 5890, Lovelace Respiratory Research Institute, Albuquerque, NM 87185. E-mail: msopori{at}lrri.org
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↵1 This work was supported in part by Grant DA04208 from the National Institute of Drug Abuse.
- Abbreviations:
- SM
- cigarette smoke
- AFC
- antibody-forming cell
- TRC
- T cell antigen receptor
- SRBC
- sheep red blood cells
- PTK
- protein tyrosine kinase
- PLC
- phospholipase C
- IP3
- inositol-1,4,5-trisphosphate
- PY
- phosphotyrosine
- TPM
- total particulate matter
- CON
- control
- FA
- filtered air
- mAb
- monoclonal antibody
- Received May 18, 1999.
- Accepted December 6, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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