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.
Chu
T M
TM
Department of Diagnostic Immunology Research and Biochemistry, New York State Department of Health, Buffalo 14263, USA. tmchu@sc3102.med.buffalo.edu
Kawinski
E
E
D004305:Dose-Response Relationship, Drug; D005341:Fibrinolysin / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology; D012661:Semen / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000502:physiology*; D013381:Subtilisins / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
D011480:Protease Inhibitors; D013450:Sulfones; D016212:Transforming Growth Factor beta; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D012697:Serine Endopeptidases; D013381:Subtilisins; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator