Role of Plasminogen and Urokinase-Type Plasminogen Activator in Cardiac Mesenchymal Cell Migration In Vitro

Studies show that urokinase-type plasminogen activator (uPA) conversion of plasminogen into plasmin is an important mediator of cell migration. In the developing chick 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 activation of plasminogen to plasmin increases cardiac mesenchymal cell migration in vitro. The first part of the study assessed stage 17/18 chicken AV explant lysates for their ability to convert plasminogen into plasmin. They were shown to activate chicken plasminogen and produce plasmin. The lysates did not have any detectable tissue-type plasminogen activator. Next, the AV explants were cultured on 3-dimensional collagen gels and the migratory capacity of cardiac mesenchymal cells was assessed in the presence or absence of various test reagents. Addition of human and chicken plasminogen, or aprotinin (an inhibitor of plasmin) had no effect on cell migration. However, an anticatalytic-chicken uPA antibody, but not non- immune IgG, significantly decreased cell migration at all concentrations tested. These results showed that (1) AV segments can activate plasminogen and that an anticatalytic uPA IgG can block this activity, (2) the plasminogen/plasmin system is not required for cardiac mesenchymal cell migration in vitro, and (3) uPA mediates cardiac mesenchymal cell migration in vitro independent of its ability to convert plasminogen into plasmin.Therefore, these results reject the hypothesis that uPA activation of plasminogen to plasmin increases cardiac mesenchymal cell migration in vitro.

Grantor dc:publisher

Creighton University

Year dc:date.issued

1997

Author dc:creator

• Gorny, Kristie Nicole

Advisor dc:contributor.advisor

• Brauer, Philip R.

Statement dc:rights

• Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10504/55679

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/55679