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PECAM-1 (CD31) expression modulates bleeding time in vivo
S Mahooti1, D Graesser, S Patil
1Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.
Insights
Platelet endothelial cell adhesion molecule-1 (PECAM-1) deficiency causes prolonged bleeding in mice. Endothelial PECAM-1, not platelet PECAM-1, is crucial for regulating blood clotting and preventing excessive bleeding.
Area of Science:
- Immunology
- Vascular Biology
- Hematology
Background:
- Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an Ig superfamily member expressed on blood and endothelial cells.
- PECAM-1 acts as an adhesion and signaling molecule, influencing angiogenesis, cell migration, and leukocyte transmigration.
- Previous studies suggested PECAM-1's role in thrombosis, but in vitro platelet aggregation in deficient mice showed no abnormalities.
Purpose of the Study:
- To investigate the in vivo role of PECAM-1 in bleeding and thrombosis.
- To determine whether PECAM-1's function in bleeding is mediated by hematopoietic or endothelial cells.
Main Methods:
- Assessed bleeding times in PECAM-1-deficient mice.
- Performed bone marrow transplantation experiments using wild-type and PECAM-1-deficient hematopoietic precursors and recipients.
- Evaluated the contribution of endothelial versus hematopoietic cell PECAM-1 to hemostasis.
Main Results:
- PECAM-1-deficient mice exhibited significantly prolonged in vivo bleeding times.
- Engraftment of wild-type hematopoietic precursors into PECAM-1-deficient mice did not correct the prolonged bleeding.
- Engraftment of PECAM-1-deficient hematopoietic precursors into wild-type mice resulted in normal bleeding times, indicating endothelial PECAM-1 is critical.
Conclusions:
- Endothelial cell-expressed PECAM-1 plays a critical role in modulating in vivo thrombosis and hemostasis.
- Hematopoietic cell-derived PECAM-1 is not essential for regulating bleeding times.
- These findings highlight the importance of endothelial PECAM-1 in vascular health and bleeding regulation.
Abstract:
PECAM-1 is a 130-kd member of the Ig superfamily present on endothelial cells, platelets, polymorphonuclear leukocytes, monocytes, and lymphocytes. Its expression begins early in development and persists through adulthood. PECAM-1 functions as an adhesion and signaling molecule between adjacent endothelial cells and between endothelial cells and circulating blood elements. Antibodies directed against PECAM-1 have been shown to affect angiogenesis, endothelial cell migration, and polymorphonuclear leukocyte transmigration. Furthermore, its dimerization is associated with the modulation of integrin affinity. Antibody inhibition studies suggest that PECAM-1 plays a role in modulating thrombosis; however, recent in vitro aggregation studies performed on platelets harvested from PECAM-1-deficient mice revealed no abnormalities. In this report we demonstrate prolonged in vivo bleeding times in PECAM-1-deficient mice. This abnormality was not corrected when wild-type hematopoietic precursors were engrafted into marrow-ablated PECAM-1-deficient mice. Furthermore, normal bleeding times were observed when marrow-ablated wild-type mice were engrafted with hematopoietic precursors harvested from PECAM-1-deficient mice. These studies are consistent with a role for PECAM-1 in modulating thrombosis in the vasculature, which is potentially mediated by endothelial cell PECAM-1 expression.