Abstract
Chronic exposure of rodents to nicotine via subcutaneously or intracerebroventricularly implanted miniosmotic pumps affects T cell function. However, this method of continuous nicotine administration does not replicate the self-motivated administration of nicotine in human smokers. To determine whether nicotine impairs the immune system under conditions pertinent to human smokers, we investigated the T cell responsiveness of male Lewis rats self-administering (SA) nicotine (0.03 mg/kg of body weight per injection) 40 to 50 times/day for 5 weeks, using a model of virtually unlimited access to nicotine. Compared with sham control animals, the concanavalin A-induced proliferation of spleen cells from SA rats was significantly decreased. Moreover, the ability of spleen cells to mobilize intracellular Ca2+ after ligation of the T cell antigen receptor (TCR) with an anti-αβ TCR antibody was significantly less in SA than in control rats. In addition, inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular Ca2+ stores were markedly depleted in spleen cells from SA animals. These results suggest that chronic nicotine self-administration suppresses T cell responsiveness, and this suppression may result from an impaired TCR-mediated signaling that stems from the depletion of IP3-sensitive intracellular Ca2+ stores.
Footnotes
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This study was funded in part by National Institutes of Health Grants DA-04208 (to M.L.S.), DA-03977 (to B.M.S.), and DA-04196 (to B.M.S.).
- Abbreviations:
- TCR
- T cell antigen receptor
- [Ca2+]i
- intracellular ionized calcium concentration
- IP3
- inositol 1,4,5-trisphosphate
- SA
- self-administering
- PBS
- phosphate-buffered saline
- Con A
- concanavalin A
- Ab
- antibody
- mAb
- monoclonal Ab
- Received October 17, 2001.
- Accepted March 8, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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