Plasmin, substilisin-like endoproteases, tissue plasminogen activator, and urokinase plasminogen activator are involved in activation of latent TGF-beta 1 in human seminal plasma

We reported previously that TGF-beta 1 is a major immunosuppressive agent in human seminal plasma. TGF-beta 1 in seminal plasma is so abundant that it may represent the highest physiologic concentration of TGF-beta 1 reported for a biological fluid. The in vitro activation of TGF-beta 1 is detected at acidic pH. The acidic environment of the vagina is suggested as an in vivo physiological condition for the activation of seminal plasma latent TGF-beta 1. The present study demonstrates that Pefabloc [4-(2-aminoethyl)-benzenesulfonyl fluoride AEBSF]-inhibitable serine proteases are involved in the activation of latent TGF-beta 1. Pefabloc inhibits latent TGF-beta 1 activation in a dose- and time-dependent manner. The use of other protease inhibitors and specific antibodies reveals that, in addition to plasmin, substilisin-like endoproteases and tissue- and urokinase-type plasminogen activators participate in the activation of latent TGF-beta 1 in human seminal plasma.