E-Selectin Supports Neutrophil Rolling In Vitro under Conditions of Flow

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Abstract

E-selectin was evaluated for its ability to support neutrophil adhesion under conditions of flow. At a wall shear stress of 1.85 dyn/cm2, neutrophils were found to attach to E-selectin expressed on the apical surface of L cell monolayers. The initial intercellular contact was most often evidenced by neutrophils rolling on the monolayer at a mean rate of (approximately equal) 10 microns/s. Anti-E-selectin monoclonal antibody, CL2/6, inhibited this interaction by > 90%. Rolling neutrophils often transiently stopped, but in contrast to the behavior on stimulated endothelial cells, they remained spherical in shape and did not migrate on or beneath the monolayer. A possible contribution of neutrophil L-selectin to this interaction was indicated by the findings that anti-L-selectin monoclonal antibody, DREG-56, inhibited E-selectin-dependent adhesion under flow by > 65%, and there was a highly significant correlation between surface levels of L-selectin and E-selectin-dependent adhesion under flow. E-selectin also appeared to support neutrophil adhesion to IL-1beta-stimulated endothelial cells under conditions of flow, but it accounted for only (approximately equal) 30% of the level of adherence, in contrast to L-selectin which accounted for > 65%. Thus, both L-selectin and E-selectin can support neutrophil adhesion at wall shear stresses that preclude intercellular adhesion molecule-1-dependent adhesion, and they participate in neutrophil adherence to stimulated endothelial cells under conditions of flow. (J. Clin. Invest. 1993. 92:2719-2730.) Key words: adhesion. CD18. intercellular adhesion molecule-1. neutrophils. selectins

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