Urokinase regulates embryonic cardiac cushion cell migration without converting plasminogen.
Urokinase-type plasminogen activator (uPA) activation of plasminogen is an important mediator of cell migration in many cell types. In the developing avian heart, uPA has been implicated as a mediator of atrioventricular (AV) cushion cell migration; however, the role of the plasminogen/plasmin system has not been examined. The purpose of this study was to test the hypothesis that uPA conversion of plasminogen to plasmin mediates AV cushion cell migration in vitro. Stage 17/18 chicken atrioventricular tissue lysates converted plasminogen into plasmin through uPA activity but no tissue-type plasminogen activator activity was detected. Zymograms on living cultured AV explants also activated plasminogen producing plasmin that degraded extracellular protein. The migratory capacity of cushion cells was assessed in the presence or absence of various test reagents known to alter the plasminogen/plasmin system. Addition of either human or chicken plasminogen or aprotinin (an inhibitor of plasmin) had no effect on cell migration. However, an anti-catalytic uPA antibody that blocked AV uPA activity, significantly decreased cell migration at all concentrations tested. These results showed that uPA mediated a portion of cushion cell migration in vitro. Although AV segments activated plasminogen and degraded extracellular proteins, uPA's functional role in cushion cell migration did not involve the plasminogen/plasmin system.
Gorny
K N
KN
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Brauer
P R
PR
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D046508:Culture Techniques; D005341:Fibrinolysin / Q000378:metabolism; D006325:Heart Atria / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D006352:Heart Ventricles / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010958:Plasminogen / Q000378:metabolism* / Q000494:pharmacology; D010960:Plasminogen Activators / Q000276:immunology / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
D009842:Oligopeptides; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; D010958:Plasminogen; D007611:Aprotinin; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator