Cigarette smoke suppresses in vitro allergic activation of mouse mast cells.
BACKGROUND
Mast cells are important effector cells in innate or acquired immunity that contribute to host defence. 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 pro-inflammatory 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 the 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 release of granules, production of leukotrienes, chemokines and cytokines was determined in the supernatants by ELISA. The effect of CSM exposure on intracellular signalling, especially the nuclear factor (NF)-kappaB and extracellular signal-regulated kinase (Erk)1/2 pathways, was analysed 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, activating transcription factor (ATF)-1 was phosphorylated after stimulation with IgE/Ag. LPS-activated mast cells were not influenced by CSM.


CONCLUSIONS
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.
Mortaz
E
E
Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands. e.mortaz@uu.nl
Folkerts
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Engels
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Nijkamp
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Redegeld
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D051697:Activating Transcription Factor 1 / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015550:Cell Degranulation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood*; D015289:Leukotrienes / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D012906:Smoke; D014026:Nicotiana / Q000276:immunology*
D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D016207:Cytokines; D015289:Leukotrienes; D008070:Lipopolysaccharides; D012906:Smoke; D007073:Immunoglobulin E; D048049:Extracellular Signal-Regulated MAP Kinases