The kidney is a major site of α2-antiplasmin production

Abstract

The serpin α2-antiplasmin (α2-AP) is the major circulating inhibitor of plasmin; it plays a determining role in the regulation of intravascular fibrinolysis. In addition to blood plasma, plasmin formation occurs in various organs where it is thought to fulfill a spectrum of functions not restricted to clot lysis. α2-AP is synthesized by hepatocytes, but other possible sites of production have not been investigated. To explore the potential extravascular contribution of α2-AP in the regulation of proteolysis, we have isolated the murine α2-AP cDNA and determined its mRNA distribution in adult tissues. In addition to liver, kidneys are major sites of α2-AP mRNA accumulation in the mouse. The transcript is present in epithelial cells lining the convoluted portion of proximal tubules, and its accumulation is under androgen control. Human kidneys also contain high levels of α2-AP mRNA. Moderate amounts of α2-AP mRNA are detected in other murine tissues such as muscle, intestine, central nervous system, and placenta. Our observations indicate that α2-AP can be synthesized in a number of tissues, where it could function as a distal regulator of plasmin- mediated extracellular proteolysis.