Production of two immunologically distinct plasminogen activators by human tissue in culture: abstract

Plasminogen activator is known to be produced by various human tissues in culture, the kidney yielding activator similar to that in urine, urokinase. Little is known, however, about the identity and properties of activator(s) from other tissues. The present study examines activator activity accumulating in serum-free supernates of cultures from lung, kidney, intestine, renal blood vessels, and a cell line from tumor (HeLa). Immunologic properties were examined by quenching assays, performed on fibrin plates using antisera specific for urokinase as well as antiserum to purified uterine tissue activator which showed immunologic relationship to activator from perfused cadaver limbs (vascular activator) but not to urokinase. In these assays, the activity from cultures of intestine and HeLa was not affected by antisera to urokinase but was quenched by antibodies to tissue activator. Lung and blood vessels yielded activity quenched partly (40-70%) by antiserum to urokinase end partly by antibodies to tissue activator. In studies by SDS-polycrylamide gel electrophoresis and immunoassays of gel slices on fibrin plates, urokinase-related activity from lung was located in the region of activator from kidney cultures and of high molecular weight urokinase from urine (Mr.55,000). Tissue activator-re la ted activity from lung and intestine were at approximately 65,000 and that from HeLa at 75,000 molecular weight substances. These studies indicate the production in human tissues of distinct types of plasminogen activators - one corresponding to urokinase, and other(s) related to tissue/vascular activators.