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Cigarette smoke induces β2-integrin-dependent neutrophil migration across human endothelium

Saskia A Overbeek1*, Saskia Braber1, Paul A J Henricks1, Marije Kleinjan1, Vera M Kamp2, Niki A Georgiou13, Johan Garssen13, Aletta D Kraneveld1 and Gert Folkerts1

Author Affiliations

1 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands

2 Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands

3 Danone Research - Centre for Specialised Nutrition, Wageningen, The Netherlands

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Respiratory Research 2011, 12:75  doi:10.1186/1465-9921-12-75

Published: 8 June 2011

Abstract

Background

Cigarette smoking induces peripheral inflammatory responses in all smokers and is the major risk factor for neutrophilic lung disease such as chronic obstructive pulmonary disease. The aim of this study was to investigate the effect of cigarette smoke on neutrophil migration and on β2-integrin activation and function in neutrophilic transmigration through endothelium.

Methods and results

Utilizing freshly isolated human PMNs, the effect of cigarette smoke on migration and β2-integrin activation and function in neutrophilic transmigration was studied. In this report, we demonstrated that cigarette smoke extract (CSE) dose dependently induced migration of neutrophils in vitro. Moreover, CSE promoted neutrophil adherence to fibrinogen. Using functional blocking antibodies against CD11b and CD18, it was demonstrated that Mac-1 (CD11b/CD18) is responsible for the cigarette smoke-induced firm adhesion of neutrophils to fibrinogen. Furthermore, neutrophils transmigrated through endothelium by cigarette smoke due to the activation of β2-integrins, since pre-incubation of neutrophils with functional blocking antibodies against CD11b and CD18 attenuated this transmigration.

Conclusion

This is the first study to describe that cigarette smoke extract induces a direct migratory effect on neutrophils and that CSE is an activator of β2-integrins on the cell surface. Blocking this activation of β2-integrins might be an important target in cigarette smoke induced neutrophilic diseases.