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

E.C. Soethout, A.F.G. Antonis, L.H. Ulfman, A. van Hoek, R.G. van der Most, K.E. Muller, V. Rutten

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    2 Citations (Scopus)

    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 ß2-integrins, alternative integrins such as the ¿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)-¿ activated pulmonary endothelium was investigated under flow conditions in vitro. For neutrophils obtained from healthy animals, inhibition of the ß2-integrin reduced firm adhesion to 63% and inhibition of ¿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 ß2-integrin and was significantly augmented to 2·5-fold by blocking both ¿4- and ß2-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 ¿4- and ß2-integrins, indicating that these integrins did not support neutrophil rolling. In addition, the inhibition of firm adhesion by blocking both ¿4- and ß2-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 ¿4- and ß2-integrins. These results demonstrate an important function for ¿4- and ß2-integrins in rolling and firm adherence of bovine neutrophils, to TNF-¿-activated endothelium and show the dynamic use of these integrins for adhesion and migration by neutrophils in the course of BRSV infection.
    Original languageEnglish
    Pages (from-to)388-395
    JournalClinical and Experimental Immunology
    Volume138
    Issue number3
    DOIs
    Publication statusPublished - 2004

    Keywords

    • endothelial-cells
    • tnf-alpha
    • leukocyte transmigration
    • pasteurella-haemolytica
    • pulmonary inflammation
    • flow conditions
    • ifn-gamma
    • integrin
    • migration
    • deficiency

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