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.