Induction of interactions between CD44 and hyaluronic acid by a short exposure of human T cells to diverse pro-inflammatory mediators

Migration of T cells into extravascular sites of inflammation is mediated b y cell-cell and cell-matrix adhesion receptors, including the hyaluronan-bi nding glycoprotein, CD44. The biochemical nature of CD44 variants and the l igand specificity, function and the regulation of activation of CD44 expres sed on various cell types have been extensively studied. However, little is still known about the short-term influence of cytokines and chemokines on the activation of CD44 on human T cells. Therefore, we studied the role of inflammatory mediators in regulating the adhesion of T cells from human per ipheral blood to immobilized hyaluronan under static or shear stress condit ions. We found that the CD44-dependent adhesion, under static and shear str ess (i.e. relative gradual resistance to flow of 150 and 1500 s(-1)) condit ions, of T cells to hyaluronan requires a T-cell activation of 2-3 hr and i s regulated by the cross-linking of CD3, cytokines (e.g. interleukin-2 and tumour necrosis factor-alpha), and chemokines (e.g. MIP-1 beta, interleukin -8, and RANTES). This T-cell adhesion was manifested by polarization, sprea ding and co-localization of cell surface CD44 with a rearranged actin cytos keleton in hyaluronan-bound T cells. Thus, cytokines and chemokines present in the vicinities of blood vessel walls or present intravascularly in tiss ues where immune reactions take place, can rapidly activate the CD44 molecu les expressed on T cells.