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Published online before print December 21, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0907625

Received for publication September 12, 2007.
Revised November 6, 2007.
Accepted for publication November 23, 2007.

Article

Cigarette smoke stimulates the production of chemokines in mast cells

Esmaeil Mortaz ^*, Frank A. Redegeld ^*, Hadi Sarir ^*, Khalil Karimi , Danielle Raats ^*, Frans P. Nijkamp ^*, and Gert Folkerts ^*

*Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, Utrecht, The Netherlands; Department of Basic Science, Section of Biochemistry, Faculty of Veterinary Medicine, Urmia University, Iran; and Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Ontario, Canada

	Abstract

Abstract:

Chronic obstructive pulmonary disease is a major health problem and will become the third largest cause of death in the world by 2020. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular, cigarette smoke (CS), causes the progressive airflow limitation, in which macrophages and neutrophils are attracted by chemokines, leading to oxidative stress, emphysema, small airways fibrosis, and mucus hypersecretion. Smoking is also associated with an increase in mast cell numbers in bronchial mucosa. This study was conducted to determine the direct effects of CS on mast cell function, using murine bone marrow-derived mast cells (BMMC) as an in vitro model. BMMC were cultured from BALB/cBy mice for 3 weeks. Cells were treated with CS medium (CSM) for 30 min or 16 h. The effects of CSM on mast cell degranulation and chemokine production were measured. Moreover, we investigated the effect of CSM on IB- degradation and p38, Erk1/2, p65, and CREB expression by Western blotting. We found that CSM stimulated the release of chemokines in a noncytotoxic manner but did not induce mast cell degranulation. CSM induced phosphorylation of Erk1/2, p38, and CREB and increased translocation of p65 without degradation of IB- NF-B in mast cells. The induction of chemokine production by CSM in mast cells could promote and prolong the inflammatory process. Our observations suggest that mast cells may contribute to the pathogenesis of emphysema through a direct effect of CS on the production of proinflammatory chemokines.

Key Words: bone marrow-derived mast cells • COPD • thioredoxin