1. Using a skin contact hypersensitivity model (DTH), examine the regulation of CD44 on lymphocytes in relation to changes in HA expression on vascular endothelium at the site; determine the contribution of the CD44/HA interaction tot he inflammatory infiltrate and response. 2. In parallel, determine the contribution of the CD44/HA interaction to the inflammatory process in a mouse model of psoriasis. 3. Examine the effect of additional cytokines in vivo and in vitro for alteration of HA expression. Background & Significance. It is clear that the specificity and regulation of adhesion of leukocytes to endothelium results from the fact that various types of adhesion receptors can act in sequential and coordinate fashion. The major steps of adhesion, established primarily for neutrophils, include a primary event during which leukocytes are engaged by the vessel wall and then retarded by a repeated transient interaction/release, called """"""""rolling"""""""". This is followed by a secondary firm adhesion of the rolling cells and subsequent transmigration (,2). Primary adhesion has been generally attributed tot he selectin family (1,3-6), while secondary (firm) adhesion is due to heterodimeric beta2 integrins (1,6). Because mechanisms of lymphocyte trafficking must accommodate the complexities of myriad subsets of distinct, sometimes tissue-specific, homing behaviors, it would not be surprising if other ligand pairs participated in lymphocyte interactions with endothelium. We have recently characterize a novel primary (rolling) interaction between lymphoid cells and adherent cultured endothelial cells (EC) which is not selectin or integrin mediated (7). Our studies indicate that this novel adhesion pathway results from the interactions between the proteoglycan core/cartilage link protein family member, CD44, and its principal ligand hyaluronate (HA).

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