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 expression is defective in patients with the Wiskott-Aldrich syndrome, was down-regulated by phorbol 12-myristate 13-acetate (PMA) on granulocytes but not on lymphocytes. However, CD43 expressed on both of these leukocyte subpopulations was down-regulated after crosslinking by anti-CD43 monoclonal antibodies, a stimulation that may simulate the effect of a natural CD43 ligand. Soluble, labeled CD43 molecules were isolated from culture supernatants of both surface-iodinated granulocytes activated by PMA and lymphocytes stimulated with anti-CD43 antibodies. Thus, in this case down-regulation represents release from the cell surface into the culture medium, rather than internalization. The apparent molecular masses of the released molecules and of soluble CD43 isolated from human serum were identical. Importantly, PMA-induced down-regulation of CD43 on granulocytes was markedly blocked both by the metalloprotease inhibitor 1,10-phenanthroline and by the serine protease inhibitors N alpha-(p-tosyl)-L-lysine chloromethyl ketone and Pefabloc SC, which inhibit two different classes of proteases, thus indicating that the release is proteolytic.
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Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Strominger
J L
JL
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000302:isolation & purification / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D015936:Complement C5a / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D019041:L-Selectin; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051917:Leukosialin; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008970:Molecular Weight; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D051917:Leukosialin; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C465014:SPN protein, human; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate