Cigarette smoke induces beta2-integrin-dependent neutrophil migration across human endothelium.

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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 beta2-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 beta2-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 beta2-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 beta2-integrins on the cell surface. Blocking this activation of beta2-integrins might be an important target in cigarette smoke induced neutrophilic diseases.
Original languageUndefined/Unknown
Pages (from-to)75
Number of pages1
JournalRespiratory Research
Volume12
Publication statusPublished - 2011

Keywords

  • Farmacie/Biofarmaceutische wetenschappen (FARM)
  • Farmacie(FARM)
  • Biomedische technologie en medicijnen
  • Immunology
  • Pharmacology
  • Overig medisch onderzoek

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