A CENTRAL ROLE FOR MICROVILLOUS RECEPTOR PRESENTATION IN LEUKOCYTE ADHESION UNDER FLOW

Leukocyte adhesion to endothelium requires specialized mechanisms for contact initiation under flow, L-selectin (CD62L), an efficient initia tor of adhesion, is clustered on the tips of leukocyte microvilli. To test whether microvillous presentation is critical for contact formati on (''tethering''), we transfected lymphoid cells with chimeras of L-s electin and CD44, an adhesion molecule that is excluded from microvill i, CD44 transmembrane and intracellular (TM-IC) domains targeted the L -selectin ectodomain to the planar body, whereas L-selectin TM-IC segm ents conferred CD44 ectodomain clustering on microvilli. Wild-type and chimeric transfectants bound similarly to anti-ectodomain MAbs in sta tic assays, but MAb binding under Row was much more efficient in the c ontext of microvillous presentation, Similarly, wild-type and chimeric L-selectin possessed equivalent lectin activity, but microvillous pre sentation dramatically enhanced contact initiation on a native ligand. These findings demonstrate a critical role for receptor topography in leukocyte adhesion and suggest a novel regulatory mechanism of leukoc yte trafficking.