title: Bovine respiratory syncytial virus infection influences the impact of alpha- and beta-integrin-mediated adhesion of peripheral blood neutrophils.
abstract: Neutrophil migration into the airways and pulmonary tissue is a common finding in bovine respiratory syncytial virus (BRSV) infections. Although neutrophil trans-endothelial migration in general depends on beta2-integrins, alternative integrins such as the alpha4-integrins have been implicated. In this study, rolling and firm adhesion of peripheral blood neutrophils isolated from healthy and BRSV-infected calves to tumour necrosis factor (TNF)-alpha activated pulmonary endothelium was investigated under flow conditions in vitro. For neutrophils obtained from healthy animals, inhibition of the beta2-integrin reduced firm adhesion to 63% and inhibition of alpha4-integrin to 73% compared with untreated controls. Inhibition of both integrins reduced firm adhesion to 25%. Rolling velocity, which is used as a parameter for integrin involvement in neutrophil rolling, increased 1.7-fold by blocking beta2-integrin and was significantly augmented to 2.5-fold by blocking both alpha4- and beta2-integrins. For neutrophils obtained from BRSV-infected animals, however, rolling velocities at 10 days after infection (p.i.) were not influenced by blocking adhesion of alpha4- and beta2-integrins, indicating that these integrins did not support neutrophil rolling. In addition, the inhibition of firm adhesion by blocking both alpha4- and beta2-integrins was reduced significantly 9 days post-infection, resulting in a residual 68% neutrophil binding at 9 days p.i. Non-blocked firm adherence was not reduced, indicating that binding was achieved by other mechanisms than through alpha4- and beta2-integrins. These results demonstrate an important function for alpha4- and beta2-integrins in rolling and firm adherence of bovine neutrophils, to TNF-alpha-activated endothelium and show the dynamic use of these integrins for adhesion and migration by neutrophils in the course of BRSV infection.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. ernst.soethout@nvi-vaccin.nl [corrected]
authors.forename: E C
authors.initials: EC
authors.lastname: Soethout
authors.forename: A F G
authors.initials: AF
authors.lastname: Antonis
authors.forename: L H
authors.initials: LH
authors.lastname: Ulfman
authors.forename: A
authors.initials: A
authors.lastname: Hoek
authors.forename: R G
authors.initials: RG
authors.lastname: van der Most
authors.forename: K E
authors.initials: KE
authors.lastname: Müller
authors.forename: V P M G
authors.initials: VP
authors.lastname: Rutten
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002417:Cattle; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology; D039001:Integrin alpha Chains / Q000037:antagonists & inhibitors / Q000276:immunology; D039641:Integrin beta Chains / Q000276:immunology; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D016023:Integrins