REGULATORY ROLE OF CD43 LEUKOSIALIN ON INTEGRIN-MEDIATED T-CELL ADHESION TO ENDOTHELIAL AND EXTRACELLULAR-MATRIX LIGANDS AND ITS POLAR REDISTRIBUTION TO A CELLULAR UROPOD

CD43 is a cell surface-associated mucin that is abundantly expressed b y most leukocytes, and that appears to function as a negative regulato r of cell surface interactions, providing a repulsive barrier around c ells. We have analyzed herein the ability of anti-CD43 monoclonal anti body (MoAb) to upregulate both beta 1 and beta 2 integrin-mediated cel l adhesion and to promote redistribution of the CD43 molecule into a c ellular uropod, Engagement of CD43 with specific antibodies enhanced t he cell adhesion to both 80- and 38-kD fibronectin fragments as well a s to the endothelial cell ligands vascular cell adhesion molecule-1 an d intercellular adhesion molecule-1, an effect that was mediated throu gh the alpha 5 beta 1, alpha 4 beta 1, and alpha L beta 2 integrins, r espectively. This effect on cell adhesion was achieved in Jurkat leuke mic T cells by anti-cD43 MoAb alone; however, in T lymphoblasts, the a ctivation of cell adhesion required the concomitant ligation of CD3 wi th suboptimal doses of anti-CD3 MoAb. Immunofluorescence analysis show ed that the engagement of CD43 was accompanied by a differential redis tribution of CD43 into a well-defined cytoplasmic projection or uropod , whereas the beta 1 or beta 2 integrins remained uniformly located on the contact area with substrata. This change in the localization of C D43 did not require costimulation and was induced directly by engageme nt of CD43 in T lymphoblasts. Other stimuli of cell adhesion in the fo rm of cross-linked anti-CD3 MoAb or phorbol esters did not induce urop od formation or CD43 redistribution. In addition, we observed that pro longed coculture of resting peripheral blood T lymphocytes with endoth elial cells, in the absence of anti-CD43 MoAb, induced uropod formatio n and redistribution of CD43 in T cells. Interestingly, the myosin-dis rupting drug butanedione monoxime inhibited the redistribution of CD43 induced by the specific MoAb, whereas the stimulation of cell adhesio n induced by engagement of CD43 was preserved in the presence of this drug. These observations indicate that the signaling inducing integrin -mediated cell adhesion by CD43 takes place independently from the rec eptor redistribution, Altogether, these results indicate that CD43 has a regulatory role on both integrin-mediated T-cell adhesion and cellu lar morphology. (C) 1995 by The American Society of Hematology.