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

Clin Exp Immunol. 2004 Dec;138(3):388-95. doi: 10.1111/j.1365-2249.2004.02639.x.

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Cattle
  • Cell Adhesion / immunology
  • Cell Adhesion Molecules / immunology
  • Cell Movement / immunology
  • Cells, Cultured
  • Endothelial Cells / immunology
  • Integrin alpha Chains / antagonists & inhibitors
  • Integrin alpha Chains / immunology
  • Integrin beta Chains / immunology
  • Integrins / antagonists & inhibitors
  • Integrins / immunology*
  • Neutrophils / immunology*
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus, Bovine / immunology*

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Integrin alpha Chains
  • Integrin beta Chains
  • Integrins