Hindawi Publishing Corporation Mediators of Infammation Volume 2013, Article ID 813091, 7 pages http://dx.doi.org/10.1155/2013/813091 Research Article Cigarette Smoke Suppresses the Surface Expression of c-kit and FcRI on Mast Cells M. E. Givi, 1 B. R. Blokhuis, 1 C. A. Da Silva, 2 I. Adcock, 3 J. Garssen, 1,4 G. Folkerts, 1 F. A. Redegeld, 1 and E. Mortaz 1,5 1 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, Te Netherlands 2 Integrative Pharmacology, Department of Biosciences, AstraZeneca R&D Lund Respiratory and Infammation Research Area, 22 187 Lund, 43183 M¨ olndal, Sweden 3 Airways Disease Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK 4 Danone Research-Centre for Specialised Nutrition, P.O. Box 7005, 6700 CA Wageningen, Te Netherlands 5 Department of Immunology, Chronic Respiratory Disease Research Center and National Research Institute of Tuberculosis and Lung Disease (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, P.O. Box 19575/154, Tehran, Iran Correspondence should be addressed to E. Mortaz; e.mortaz@uu.nl Received 18 October 2012; Revised 1 January 2013; Accepted 2 January 2013 Academic Editor: F´ abio Santos Lira Copyright © 2013 M. E. Givi et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chronic obstructive pulmonary disease (COPD) is a multicomponent disease characterized by emphysema and/or chronic bronchitis. COPD is mostly associated with cigarette smoking. Cigarette smoke contains over 4,700 chemical compounds, including free radicals and LPS (a Toll-Like Receptor 4 agonist) at concentrations which may contribute to the pathogenesis of diseases like COPD. We have previously shown that short-term exposure to cigarette smoke medium (CSM) can stimulate several infammatory cells via TLR4 and that CSM reduces the degranulation of bone-marrow-derived mast cells (BMMCs). In the current study, the efect of CSM on mast cells maturation and function was investigated. Coculturing of BMMC with CSM during the development of bone marrow progenitor cells suppressed the granularity and the surface expression of c-kit and FcRI receptors. Stimulation with IgE/antigen resulted in decreased degranulation and release of T1 and T2 cytokines. Te efects of CSM exposure could not be mimicked by the addition of LPS to the culture medium. In conclusion, this study shows that CSM may afect mast cell development and subsequent response to allergic activation in a TLR4-independent manner. 1. Introduction Te incidence of chronic respiratory diseases like chronic obstructive pulmonary disease (COPD) and asthma is increasing dramatically and currently afect the lives of approximately 300 and 200 million people, respectively, worldwide [1, 2]. COPD is characterized by a complex inter- action between infammatory and structural cells, all of which have the capacity to release multiple infammatory mediators [3]. Cigarette smoke (CS) is the major player in the pathogen- esis of COPD [3]. Exposure to CS activates an infammatory cascade in the airways resulting in the production of a num- ber of potent cytokines and chemokines with accompanying damage to the lung epithelium, increased permeability, and recruitment of macrophages and neutrophils [4]. CS contains high levels of reactive oxygen species [5] and LPS [6, 7]. LPS is a strong Toll-Like Receptor (TLR) 4 agonist [8]. TLRs are an evolutionarily conserved family of cell surface molecules which participate in innate immune response [9, 10]. Te efects of smoking on infammatory cell maturation and diferentiation have not been well described. Upon encountering pathogens and/or proinfammatory mediators, cells undergo a transformation process termed “matura- tion,” which, for example, enhances dendritic cell (DC) Ag-presenting capacity or ability to release infammatory cytokines. Te role of TLRs in maturation and development