TY - JOUR
T1 - Bovine respiratory syncytial virus infection influences the impact of α4- and β2-integrin-mediated adhesion of peripheral blood neutrophils
AU - Soethout, E.C.
AU - Antonis, A.F.G.
AU - Ulfman, L.H.
AU - Hoek, A.
AU - Van Der Most, R.G.
AU - Müller, K.E.
AU - Rutten, V.P.M.G.
PY - 2004
Y1 - 2004
N2 - 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 β2-integrins, alternative integrins such as the α4-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 β2-integrin reduced firm adhesion to 63% and inhibition of α4-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 β2-integrin and was significantly augmented to 2·5-fold by blocking both α4- and β2-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 α4- and β2-integrins, indicating that these integrins did not support neutrophil rolling. In addition, the inhibition of firm adhesion by blocking both α4- and β2-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 α4- and β2-integrins. These results demonstrate an important function for α4- and β2-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.
AB - 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 β2-integrins, alternative integrins such as the α4-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 β2-integrin reduced firm adhesion to 63% and inhibition of α4-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 β2-integrin and was significantly augmented to 2·5-fold by blocking both α4- and β2-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 α4- and β2-integrins, indicating that these integrins did not support neutrophil rolling. In addition, the inhibition of firm adhesion by blocking both α4- and β2-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 α4- and β2-integrins. These results demonstrate an important function for α4- and β2-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.
KW - Diergeneeskunde (DGNK)
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-9644302275&partnerID=MN8TOARS
U2 - 10.1111/j.1365-2249.2004.02639.x
DO - 10.1111/j.1365-2249.2004.02639.x
M3 - Article
SN - 0009-9104
VL - 138
SP - 388
EP - 395
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 3
ER -