A role for plasmin in platelet aggregation: differential regulation of IGF release from IGF-IGFBP complexes?
OBJECTIVE
To determine if plasmin differentially augments platelet aggregation through variable efficiencies of IGF-IGFBP complex cleavage.


METHODS
We utilized ADP-triggered platelet aggregation assays to test the effects of IGF-I versus IGF-II in complex with IGFBP-2 or IGFBP-3 upon the efficiency of plasmin (a known IGFBP protease) as a pro-aggregatory stimulus. In vitro proteolysis assays were performed as controls.


RESULTS
We found that IGF-I complexes augmented platelet-mediated aggregation whereas IGF-II either had no effect (IGFBP-2) or inhibited platelet-mediated aggregation (IGFBP-3). In vitro proteolysis assays of IGFBP-2 and IGFBP-3 using plasmin revealed that three of the four aggregation findings were explained by the disparate efficiencies of IGFBP proteolysis associated with each IGF. Only IGF-II-IGFBP-2 complex resulted in a finding that could not be explained by the concept of differential regulation of plasmin's proteolysis efficiency by the two IGF ligands.


CONCLUSIONS
Our findings demonstrate that the plasmin can differentially modulate platelet aggregation in response to intrinsic heterogeneities within the IGF axis.
Marcinkiewicz
Marek
M
University of Virginia Children's Hospital, Department of Pediatrics, P.O. Box 800386, Charlottesville, VA 22908, USA.
Gordon
Phillip V
PV
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013002:Somatomedins / Q000378:metabolism*
D018969:Insulin-Like Growth Factor Binding Proteins; D046912:Multiprotein Complexes; D013002:Somatomedins; D005341:Fibrinolysin; D007213:Indomethacin