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Originally published online as doi:10.1189/jlb.0907625 on December 21, 2007

Published online before print December 21, 2007
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(Journal of Leukocyte Biology. 2008;83:575-580.)
© 2008 by Society for Leukocyte Biology

Cigarette smoke stimulates the production of chemokines in mast cells

Esmaeil Mortaz*,{dagger},1, Frank A. Redegeld*, Hadi Sarir*, Khalil Karimi{ddagger}, 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;
{dagger} Department of Basic Science, Section of Biochemistry, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran; and
{ddagger} Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Ontario, Canada

1Correspondence: Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands. E-mail: e.mortaz{at}uu.nl

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 I{kappa}B-{alpha} 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 I{kappa}B-{alpha} NF-{kappa}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