CD43, THE MAJOR SIALOGLYCOPROTEIN OF HUMAN-LEUKOCYTES, IS PROTEOLYTICALLY CLEAVED FROM THE SURFACE OF STIMULATED LYMPHOCYTES AND GRANULOCYTES

CD43, the major Sialoglycoprotein of human leukocytes, whose expressio n is defective in patients with the Wiskott-Aldrich syndrome, was down -regulated by phorbol 12-myristate 13-acetate (PMA) on granulocytes bu t not on lymphocytes. However, CD43 expressed on both of these leukocy te subpopulations was down-regulated after crosslinking by anti-CD43 m onoclonal antibodies, a stimulation that may simulate the effect of a natural CD43 ligand. Soluble, labeled CD43 molecules were isolated fro m culture supernatants of both surface-iodinated granulocytes activate d by PMA and lymphocytes stimulated with anti-CD43 antibodies. Thus, i n this case down-regulation represents release from the cell surface i nto the culture medium, rather than internalization. The apparent mole cular masses of the released molecules and of soluble CD43 isolated fr om human serum were identical. Importantly, PMA-induced down-regulatio n of CD43 on granulocytes was markedly blocked both by the metalloprot ease inhibitor 1,10-phenanthroline and by the serine protease inhibito rs N(alpha)-(p-tosyl)-L-lysine chloromethyl ketone and Pefabloc SC, wh ich inhibit two different classes of proteases, thus indicating that t he release is proteolytic.