title: Effect of cigarette smoke extract on dendritic cells and their impact on T-cell proliferation.
abstract: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Cigarette smoke has been considered a major player in the pathogenesis of COPD. The inflamed airways of COPD patients contain several inflammatory cells including neutrophils, macrophages,T lymphocytes, and dendritic cells (DCs). The relative contributions of these various inflammatory cells to airway injury and remodeling are not well documented. In particular, the potential role of DCs as mediators of inflammation in the smoker's airways and COPD patients is poorly understood. In the current study we analyzed the effects of cigarette smoke extract on mouse bone marrow derived DC and the production of chemokines and cytokines were studied. In addition, we assessed CSE-induced changes in cDC function in the mixed lymphocyte reaction (MLR) examining CD4+ and CD8+ T cell proliferation. Cigarette smoke extract induces the release of the chemokines CCL3 and CXCL2 (but not cytokines), via the generation of reactive oxygen species (ROS). In a mixed-leukocyte reaction assay, cigarette smoke-primed DCs potentiate CD8(+)T cell proliferation via CCL3. In contrast, proliferation of CD4(+)T cells is suppressed via an unknown mechanism. The cigarette smoke-induced release of CCL3 and CXCL2 by DCs may contribute to the influx of CD8(+)T cells and neutrophils into the airways, respectively.
authors.affiliation: Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. e.mortaz@uu.nl
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mortaz
authors.forename: Aletta D
authors.initials: AD
authors.lastname: Kraneveld
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Smit
authors.forename: Mirjam
authors.initials: M
authors.lastname: Kool
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: Frans P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018925:Chemokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D012906:Smoke; D013601:T-Lymphocytes / Q000166:cytology*; D014026:Nicotiana
chemical_list: D018925:Chemokines; D012906:Smoke