The intracellular serpin proteinase inhibitor 6 is expressed in monocytes and granulocytes and is a potent inhibitor of the azurophilic granule protease, cathepsin G

The monocyte and granulocyte azurophilic granule proteinases elastase. prot einase 3, and cathepsin G are implicated in acute and chronic diseases thou ght to result from an imbalance between the secreted proteinase(s) and circ ulating serpins such as alpha 1-proteinase inhibitor and alpha 1-antichymot rypsin. We show here that the intracellular serpin, proteinase inhibitor 6 (PI-6). is present in monocytes, granulocytes. and myelomonocytic cell line s. In extracts from these cells, PI-6 bound an endogenous membrane-associat ed serine proteinase to form an sodium dodecyl sulfate (SDS)-stable complex . Using antibodies to urokinase, elastase, proteinase 3. or cathepsin G, we demonstrated that the complex contains cathepsin G. Native cathepsin G and recombinant PI-6 formed an SDS-stable complex in vitro similar in size to that observed in the extracts. Further kinetic analysis demonstrated that c athepsin G and PI-6 rapidly form a tight 1:1 complex (k(a) = 6.8 +/- 0.2 x 10(6) mol/L(-1)s(-1) at 17 degrees C; K-i = 9.2 +/- 0.04 x 10(-10) mol/L). We propose that PI-6 complements alpha 1-proteinase inhibitor and alpha 1-a ntichymotrypsin (which control extracellular proteolysis) by neutralizing c athepsin G that leaks into the cytoplasm of monocytes or granulocytes durin g biosynthesis or phagocytosis. Control of intracellular cathepsin G may be particularly important, because it has recently been shown to activate the proapoptotic proteinase,caspase-7. (C) 1999 by The American Society of Hem atology.