Inhibition of lymphocyte protease granzyme A by antithrombin III.
T-lymphocytes contain a cytoplasmic granule associated homo-dimeric protease designated granzyme A. Upon T-cell target cell interaction, the granules undergo exocytosis and granzyme A, and other granule constituents, are released. Here we show that granzyme A secreted into plasma is immediately inactivated by antithrombin III. The rate of complex formation is enhanced 400-fold in the presence of heparin. Two different complexes are generated: granzyme A-antithrombin III and granzyme A-(antithrombin III)2, respectively, indicating that both active centers of granzyme A are functional. Thus, the proteolytic activity of lymphocyte protease granzyme A, whose physiologically relevant function is unknown, is well regulated in plasma.
Masson
D
D
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Tschopp
J
J
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D001769:Blood; D002478:Cells, Cultured; D053804:Granzymes; D006493:Heparin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology*
D015842:Serine Proteinase Inhibitors; D000990:Antithrombin III; D006493:Heparin; D053804:Granzymes; D012697:Serine Endopeptidases