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(Circulation. 2003;107:604.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Nicotine Strongly Activates Dendritic Cell–Mediated Adaptive Immunity

Potential Role for Progression of Atherosclerotic Lesions

Alexandra Aicher, MD^*; Christopher Heeschen, MD^*; Mariette Mohaupt, PhD; John P. Cooke, MD, PhD; Andreas M. Zeiher, MD; Stefanie Dimmeler, PhD

From the Department of Internal Medicine IV, Molecular Cardiology, University of Frankfurt, Germany (A.A., C.H., A.M.Z., S.D.); the Department of Molecular Immunology and Gene Therapy, Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany (M.M.); and the Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, Calif (J.P.C.).

Correspondence to Stefanie Dimmeler, PhD, Department of Molecular Cardiology, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail Dimmeler{at}em.uni-frankfurt.de

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^-8 to 10^-4 mol/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 T_H1 cytokine interleukin-12 by human DCs. These effects were abrogated by the nicotinic receptor antagonist -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.

Key Words: cells • immunity • atherosclerosis

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