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

J Pharmacol Exp Ther. 2000 Apr;293(1):166-71.

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-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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody-Producing Cells / drug effects
  • Antigens / immunology
  • Calcium / metabolism*
  • Cotinine / blood
  • Enzyme Activation / drug effects
  • Female
  • Health Status
  • Immunity / drug effects*
  • Inositol 1,4,5-Trisphosphate / physiology*
  • Isoenzymes / metabolism
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Phospholipase C gamma
  • Plants, Toxic*
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptor-CD3 Complex, Antigen, T-Cell / drug effects
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Smoke / adverse effects*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tobacco*
  • Type C Phospholipases / metabolism

Substances

  • Antigens
  • Isoenzymes
  • Nicotinic Agonists
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Smoke
  • Nicotine
  • Inositol 1,4,5-Trisphosphate
  • Protein-Tyrosine Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • Cotinine
  • Calcium