The α4-integrin supports leukocyte rolling and adhesion in vivo

α4-integrin has been implicated in the recruitment of peripheral blood mononuclear cells (PBMCs) to sites of inflammation. In this study we used a model wherein intravital microscopy could be used to characterize the type of adhesive interactions mediated by α4-integrin in vivo. As early as 4 days after immunization with As. butyricum, mast cell reactivity was altered, and rats developed a systemic vasculitis characterized by large increases in the number of rolling (150±15 vs. 33±7 control) and adherent (18±3 vs. 5±0.4 control) leukocytes within mesenteric venules. The selectins could only account for -55% of the leukocyte rolling while a monoclonal antibody (mAb) against the α4-integrin eliminated the remaining rolling. Anti-α4 therapy also eliminated the increase in leukocyte adhesion observed in this model, while selectin therapies and an anti-CD 18 mAb did not reduce adhesion. A serum against polymorphonuclear leukocytes (PMNs) confirmed that a significant proportion of rolling and adhering cells were PBMCs. Sequential treatment with anti-PMN serum and the anti-α4 mAb demonstrated that α4-dependent rolling was distinct from PMN rolling populations. The anti-α4 mAb did not reduce the initial leukocyte tethering in this model, whereas an anti-Lselectin mAb reduced tethering by 52±6%. These data suggest that α4 can mediate both rolling and adhesion in the multi-step recruitment of PMBCs in vivo, and these interactions can occur independent of the selectins and β₂-integrins.