Bovine respiratory syncytial virus infection influences the impact of α(4)- and β(2)-integrin-mediated adhesion of peripheral blood neutrophils

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 β(2)-integrins, alternative integrins such as the α(4)-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)-α activated pulmonary endothelium was investigated under flow conditions in vitro. For neutrophils obtained from healthy animals, inhibition of the β(2)-integrin reduced firm adhesion to 63% and inhibition of α(4)-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 β(2)-integrin and was significantly augmented to 2·5-fold by blocking both α(4)- and β(2)-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 α(4)- and β(2)-integrins, indicating that these integrins did not support neutrophil rolling. In addition, the inhibition of firm adhesion by blocking both α(4)- and β(2)-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 α(4)- and β(2)-integrins. These results demonstrate an important function for α(4)- and β(2)-integrins in rolling and firm adherence of bovine neutrophils, to TNF-α-activated endothelium and show the dynamic use of these integrins for adhesion and migration by neutrophils in the course of BRSV infection

Anwendung der Erkenntnisse KREV an konkreten Bauvorhaben. KREV-A Teilobjekt: Stiftung Liebenau. Schlussbericht

See also BMFT-FB-T--83-270; 83-271; 83-272. With 9 refs., 84 tabs., 78 figs.SIGLEDEGerman