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Aicher, A., Heeschen, C., Mohaupt, M., Cooke, J.P., Zeiher, A.M. and Dimmeler, S., 2003. Nicotine strongly activates dendritic cell-mediated adaptive immunity - potential role for progression of atherosclerotic lesions. Circulation, 107 (4), pp. 604-611. ISSN 0009-7322
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Abstract
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 TH1 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.
| Item Type: | Journal article | ||||
|---|---|---|---|---|---|
| Publication Title: | Circulation | ||||
| Creators: | Aicher, A., Heeschen, C., Mohaupt, M., Cooke, J.P., Zeiher, A.M. and Dimmeler, S. | ||||
| Publisher: | American Heart Association | ||||
| Date: | 2003 | ||||
| Volume: | 107 | ||||
| Number: | 4 | ||||
| ISSN: | 0009-7322 | ||||
| Identifiers: |
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| Divisions: | Schools > School of Science and Technology | ||||
| Record created by: | EPrints Services | ||||
| Date Added: | 09 Oct 2015 11:04 | ||||
| Last Modified: | 23 Aug 2016 09:13 | ||||
| URI: | https://irep.ntu.ac.uk/id/eprint/22296 |
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