title: Cigarette smoke induces β2-integrin-dependent neutrophil migration across human endothelium.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands. S.A.Overbeek@uu.nl
authors.forename: Saskia A
authors.initials: SA
authors.lastname: Overbeek
authors.forename: Saskia
authors.initials: S
authors.lastname: Braber
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Henricks
authors.forename: Marije
authors.initials: M
authors.lastname: Kleinjan
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kamp
authors.forename: Niki A
authors.initials: NA
authors.lastname: Georgiou
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: Aletta D
authors.initials: AD
authors.lastname: Kraneveld
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012906:Smoke; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D018821:CD18 Antigens; C509295:ITGAM protein, human; D016177:Macrophage-1 Antigen; D012906:Smoke; D005340:Fibrinogen