Published Online
on January 27, 2003

A more recent version of this article appeared on February 4, 2003

This Article Full Text (PDF) All Versions of this Article: 107/4/604    most recent 01.CIR.0000047279.42427.6Dv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aicher, A. Articles by Dimmeler, S. Search for Related Content PubMed PubMed Citation Articles by Aicher, A. Articles by Dimmeler, S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NICOTINE NICOTINE TARTRATE Related Collections Pathophysiology

Submitted on September 3, 2002
Revised on October 17, 2002
Accepted on October 28, 2002

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, and 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.).

^* To whom correspondence should be addressed. 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

This article has been cited by other articles:

				E. Nizri, M. Irony-Tur-Sinai, O. Lory, A. Orr-Urtreger, E. Lavi, and T. Brenner Activation of the Cholinergic Anti-Inflammatory System by Nicotine Attenuates Neuroinflammation via Suppression of Th1 and Th17 Responses J. Immunol., November 15, 2009; 183(10): 6681 - 6688. [Abstract] [Full Text] [PDF]

				J. A. Poole, G. M. Thiele, N. E. Alexis, A. M. Burrell, C. Parks, and D. J. Romberger Organic dust exposure alters monocyte-derived dendritic cell differentiation and maturation Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L767 - L776. [Abstract] [Full Text] [PDF]

				A. Prasse, M. Stahl, G. Schulz, G. Kayser, L. Wang, K. Ask, J. Yalcintepe, A. Kirschbaum, E. Bargagli, G. Zissel, et al. Essential Role of Osteopontin in Smoking-Related Interstitial Lung Diseases Am. J. Pathol., May 1, 2009; 174(5): 1683 - 1691. [Abstract] [Full Text] [PDF]

				E. Ibeas, L. Fuentes, R. Martin, M. Hernandez, and M. L. Nieto Secreted phospholipase A2 type IIA as a mediator connecting innate and adaptive immunity: new role in atherosclerosis Cardiovasc Res, January 1, 2009; 81(1): 54 - 63. [Abstract] [Full Text] [PDF]

				P. R. Kroening, T. W. Barnes, L. Pease, A. Limper, H. Kita, and R. Vassallo Cigarette Smoke-Induced Oxidative Stress Suppresses Generation of Dendritic Cell IL-12 and IL-23 through ERK-Dependent Pathways J. Immunol., July 15, 2008; 181(2): 1536 - 1547. [Abstract] [Full Text] [PDF]

				M. Tsoumakidou, I. K. Demedts, G. G. Brusselle, and P. K. Jeffery Dendritic Cells in Chronic Obstructive Pulmonary Disease: New Players in an Old Game Am. J. Respir. Crit. Care Med., June 1, 2008; 177(11): 1180 - 1186. [Abstract] [Full Text] [PDF]

				C. S. Robbins, F. Franco, M. Mouded, M. Cernadas, and S. D. Shapiro Cigarette Smoke Exposure Impairs Dendritic Cell Maturation and T Cell Proliferation in Thoracic Lymph Nodes of Mice J. Immunol., May 15, 2008; 180(10): 6623 - 6628. [Abstract] [Full Text] [PDF]

				E. A. Van Vre, H. Bult, V. Y. Hoymans, V. F.I. Van Tendeloo, C. J. Vrints, and J. M. Bosmans Human C-Reactive Protein Activates Monocyte-Derived Dendritic Cells and Induces Dendritic Cell-Mediated T-Cell Activation Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 511 - 518. [Abstract] [Full Text] [PDF]

				F. G. Gao, D. F. Wan, and J. R. Gu Ex vivo Nicotine Stimulation Augments the Efficacy of Therapeutic Bone Marrow-Derived Dendritic Cell Vaccination Clin. Cancer Res., June 15, 2007; 13(12): 3706 - 3712. [Abstract] [Full Text] [PDF]

				S Ranjit and L Dazhu Potential role of dendritic cells for progression of atherosclerotic lesions. Postgrad. Med. J., September 1, 2006; 82(971): 573 - 575. [Abstract] [Full Text] [PDF]

				A. Tazi Adult pulmonary Langerhans' cell histiocytosis. Eur. Respir. J., June 1, 2006; 27(6): 1272 - 1285. [Abstract] [Full Text] [PDF]

				R. Sharma and D.-Z. Li Role of Dendritic Cells in Atherosclerosis Asian Cardiovasc Thorac Ann, April 1, 2006; 14(2): 166 - 169. [Abstract] [Full Text] [PDF]

				A. Yilmaz, C. Reiss, A. Weng, I. Cicha, C. Stumpf, A. Steinkasserer, W. G. Daniel, and C. D. Garlichs Differential effects of statins on relevant functions of human monocyte-derived dendritic cells J. Leukoc. Biol., March 1, 2006; 79(3): 529 - 538. [Abstract] [Full Text] [PDF]

				C. Bose, H. Zhang, K. B. Udupa, and P. Chowdhury Activation of p-ERK1/2 by nicotine in pancreatic tumor cell line AR42J: effects on proliferation and secretion Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G926 - G934. [Abstract] [Full Text] [PDF]

				J. Ge, Q. Jia, C. Liang, Y. Luo, D. Huang, A. Sun, K. Wang, Y. Zou, and H. Chen Advanced Glycosylation End Products Might Promote Atherosclerosis Through Inducing the Immune Maturation of Dendritic Cells Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2157 - 2163. [Abstract] [Full Text] [PDF]

				Y. V. Bobryshev Dendritic cells in atherosclerosis: current status of the problem and clinical relevance Eur. Heart J., September 1, 2005; 26(17): 1700 - 1704. [Abstract] [Full Text] [PDF]

				R. Vassallo, K. Tamada, J. S. Lau, P. R. Kroening, and L. Chen Cigarette Smoke Extract Suppresses Human Dendritic Cell Function Leading to Preferential Induction of Th-2 Priming J. Immunol., August 15, 2005; 175(4): 2684 - 2691. [Abstract] [Full Text] [PDF]

				A. C. Renkl, J. Wussler, T. Ahrens, K. Thoma, S. Kon, T. Uede, S. F. Martin, J. C. Simon, and J. M. Weiss Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype Blood, August 1, 2005; 106(3): 946 - 955. [Abstract] [Full Text] [PDF]

				Y. Iwashima, T. Katsuya, K. Ishikawa, I. Kida, M. Ohishi, T. Horio, N. Ouchi, K. Ohashi, S. Kihara, T. Funahashi, et al. Association of Hypoadiponectinemia With Smoking Habit in Men Hypertension, June 1, 2005; 45(6): 1094 - 1100. [Abstract] [Full Text] [PDF]

				P. A. VanderLaan and C. A. Reardon Thematic review series: The Immune System and Atherogenesis. The unusual suspects:an overview of the minor leukocyte populations in atherosclerosis J. Lipid Res., May 1, 2005; 46(5): 829 - 838. [Abstract] [Full Text] [PDF]

				D. Skowasch, A. Jabs, R. Andrie, S. Dinkelbach, B. Luderitz, and G. Bauriedel Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at the time of clinical in-stent restenosis Cardiovasc Res, December 1, 2003; 60(3): 684 - 691. [Abstract] [Full Text] [PDF]

				G. Bauriedel, A. Jabs, D. Skowasch, R. Hutter, J. J. Badimon, V. Fuster, U. Welsch, and B. Luderitz Dendritic cells in neointima formation after rat carotid balloon injury: coordinated expression withanti-apoptotic Bcl-2 and HSP47 in arterial repair J. Am. Coll. Cardiol., September 3, 2003; 42(5): 930 - 938. [Abstract] [Full Text] [PDF]