L-selectin (LAM-1, LEC-CAM-1, Leu-8, TQ1) is a member of the selectin family of adhesion proteins that is expressed on the surface of circulating neutrophils, monocytes, eosinophils, basophils and certain lymphocytes (1-3). Both in vivo (4-6) and in vitro (7-10) studies have indicated a role for L-selectin in mediating the initial interaction between circulating blood leukocytes and the activated endothelium under flow. Although neutrophil and lymphocyte adhesive interactions have received considerable study, much less is known about monocyte-endothelial interactions. Preliminary studies by the applicant, using a simple """"""""non- static"""""""" (rotation) adhesion assay, have demonstrated that L-selectin interacting with its inducible endothelial ligand is involved in the initial contact between human blood monocytes and TNF- or lL-4-activated HUVEC (10,11). The overall objectives of this project are to study monocyte adhesion to endothelium in various states of activation, focusing on L-selectin and its inducible endothelial ligand using a recently developed in vitro flow model, and in vivo, in an murine model of inflammation; to understand the interrelationship of this adhesion pathway with other recently characterized inducible endothelial mechanisms; and to molecularly define the peripheral vascular endothelial (i.e., non- lymphoid) ligand(s) that support L-selectin-dependent monocyte attachment under flow.
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