Nicotine Strongly Activates Dendritic Cell–Mediated Adaptive ImmunityPotential Role for Progression of Atherosclerotic Lesions
作者:
Alexandra Aicher,
Christopher Heeschen,
Mariette Mohaupt,
John Cooke,
Andreas Zeiher,
Stefanie Dimmeler,
期刊:
Circulation: Journal of the American Heart Association
(OVID Available online 2003)
卷期:
Volume 107,
issue 4
页码: 604-611
ISSN:0009-7322
年代: 2003
出版商: OVID
关键词: cells;immunity;atherosclerosis
数据来源: OVID
摘要:
Background—Antigen-presenting cells (APCs) such as monocytes and dendritic cells (DCs) stimulate T-cell proliferation and activation in the course of adaptive immunity. This cellular interaction plays a role in the growth of atherosclerotic plaques. Nicotine has been shown to increase the growth of atherosclerotic lesions. Therefore, we investigated whether nicotine can stimulate APCs and their T cell–stimulatory capacity using human monocyte–derived DCs and murine bone marrow–derived DCs as APCs.Methods and Results—Nicotine dose-dependently (10−8to 10−4mol/L) induced DC expression of costimulatory molecules (ie, CD86, CD40), MHC class II, and adhesion molecules (ie, LFA-1, CD54). Moreover, nicotine induced a 7.0-fold increase in secretion of the proinflammatory TH1 cytokine interleukin-12 by human DCs. These effects were abrogated by the nicotinic receptor antagonist &agr;-bungarotoxin and mecamylamine, respectively. The effects of nicotine were mediated in part by the phosphorylation of the PI3 kinase downstream target Akt and the mitogen-activated kinases ERK and p38 MAPK. Nicotine-stimulated APCs had a greater capacity to stimulate T-cell proliferation and cytokine secretion, as documented by mixed lymphocyte reactions and ovalbumin-specific assays with ovalbumin-transgenic DO10.11 mice. In a murine model of atherosclerosis, nicotine significantly enhanced the recruitment of DCs to atherosclerotic lesions in vivo.Conclusions—Nicotine activates DCs and augments their capacity to stimulate T-cell proliferation and cytokine secretion. These effects of nicotine may contribute to its influence on the progression of atherosclerotic lesions.
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