Role of plasminogen activators and urokinase receptor in platelet kinetics.
BACKGROUND
Plasminogen activators (PA) and plasmin are known to affect platelets but little is known of their role in platelet kinetics. We took advantage of genetically deficient mice to explore the role of urokinase (uPA) and tissue type (tPA) PAs, as well as the uPA receptor (uPAR, CD87) in platelet kinetics.


METHODS
Platelet shape and number were investigated by flow cytometry. Platelet kinetics was investigated by the in vivo biotinylation and FACS analysis. Platelet production was investigated by counting megakaryocytes in bone marrow.


RESULTS
Platelets counts were within the same range in wild type (+/+), uPA, tPA and uPAR-deficient mice. Platelet survival was similar in +/+, uPA-/-, tPA-/- but markedly reduced in uPAR-/- mice. The number of megakaryocytes in bone marrow and spleen was increased 2-3-fold in uPAR-/- compared to +/+ mice. TGF-beta mRNA level within the bone marrow was also significantly increased in uPAR-/- mice. Consistent with an increased platelet production, platelets from uPAR-/- mice had a higher RNA content, as seen by Propidium Iodide (PI) labeling and FACS analysis. Since uPAR is detectable in both hemopoietic and non-hemopoietic cells, radiation chimera were prepared. Investigation of platelet kinetics in chimera showed that platelet survival is reduced with a deficit in either bone marrow-derived, or non-hemopoietic, host cells.


CONCLUSIONS
These results demonstrate that uPAR, but not uPA or tPA, is essential for maintaining normal platelet survival. In addition, uPAR-/- mice maintain normal platelet numbers through increased production.
Piguet
P F
PF
Department of Pathology, University of Geneva, CH 1211, Switzerland. pierre.piguet@medecine.unige.ch
Vesin
C
C
Da Laperousaz
C
C
Rochat
A
A
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D005341:Fibrinolysin / Q000378:metabolism; D007700:Kinetics; D008533:Megakaryocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010960:Plasminogen Activators / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000097:blood
C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin