Activation of progelatinase B by membranes of human polymorphonuclear granulocytes

Isolated human granulocyte plasma membranes contain progelatinase B. The bi nding of progelatinase B to the membrane, however, is relatively weak, and a considerable part of progelatinase B can be removed by simply washing the membrane with buffer. This detachment does not depend on the ionic strengt h of the buffer, indicating that electrostatic forces do not play an import ant role in the binding of progelatinase B to the membrane. A complete remo val of progelatinase B is achieved by chromatography of neutrophil membrane s on gelatin-agarose. The plasma membrane of human granulocytes activates added progelatinase B. This activation is inhibited by soybean trypsin inhibitor and is thus perfo rmed by membrane bound serine proteinases. In contrast to other reports tha t claimed an important role of elastase in activating progelatinase B, we f ound that this activation is mostly inhibited by chymostatin and not by ela statinal and is thus primarily due to cathepsin G. Proteinase 3 was shown t o activate progelatinase B as efficient as neutrophil elastase, i. e. much weaker than cathepsin G. Binding of cathepsin G and elastase to the neutrop hil membrane does not change their ability to activate progelatinase B, How ever, cathepsin Gi,the most potent activator of the three neutrophil serine proteinases, is only a weak activator, when compared to stromelysin-1. Thi s, as well as only a weak binding of progelatinase B, make it doubtful that activation of membrane-bound progelatinase B by membrane-bound serine prot einases is of significant physiological importance.