Cigarette smoke suppresses in vitro allergic activation of mouse mast cells (80.1)

Abstract

Abstract Abstract Background: Mast cells are important effector cells in innate or acquired immunity that contribute to host defense. Excessive activation of mast cells can result in the development of allergic diseases, including atopic asthma. Mast cell activation by IgE and specific antigen induces the cells to release spasmogenic, vasoactive, and proinflammatory mediators, which enhance airway smooth muscle contraction, vascular permeability, and inflammatory cell recruitment. Recently, we have demonstrated that exposure of mast cells to cigarette smoke medium (CSM) triggered mast cells to produce chemokines. On the other hand, smoking may decrease the risk of allergic sensitization, which could be explained by a reduced IgE production or a diminished response of mast cells to activation of the IgE receptor. Objective: In this study, we investigated the effect of CSM on allergic activation of mast cells through IgE and antigen. Methods: Primary cultured murine mast cells were exposed to CSM and activated with IgE and antigen or lipopolysaccharide (LPS). The releases of granules, production of leukotrienes, chemokines and cytokines was determined in supernatants by ELISA. The effect of CSM exposure on intracellular signaling, especially the NF-κB and Erk1/2 pathways, was analyzed by Western blotting. Results: CSM suppressed IgE-mediated degranulation and cytokine release, but no effect was observed on leukotriene release. CSM induced phosphorylation of Erk1/2 in mast cells. In CSM-exposed mast cells ATF-1 was phosphorylated after stimulation with IgE/Ag. LPS activated mast cells were not influenced by CSM. Conclusion: Our study suggests that exposure to cigarette smoke may lead to a reduced allergic activation of mast cells without affecting their response to activation via e.g. bacterial derived LPS.