Complex interactions between platelets and activated endothelium occur during the thrombo-inflammatory reaction at sites of
vascular injuries and during vascular hemostasis. The endothelial receptor
endoglin is involved in
inflammation through
integrin-mediated leukocyte adhesion and transmigration; and heterozygous mutations in the
endoglin gene cause
hereditary hemorrhagic telangiectasia type 1. This
vascular disease is characterized by a
bleeding tendency that is postulated to be a consequence of
telangiectasia fragility rather than a platelet defect, since platelets display normal functions in vitro in this condition. Here, we hypothesize that
endoglin may act as an adhesion molecule involved in the interaction between endothelial cells and platelets through
integrin recognition. We find that the extracellular domain of human
endoglin promotes specific platelet adhesion under static conditions and confers resistance of adherent platelets to detachment upon exposure to flow. Also, platelets adhere to confluent endothelial cells in an
endoglin-mediated process. Remarkably, Chinese hamster ovary cells ectopically expressing the human αIIbβ3
integrin acquire the capacity to adhere to myoblast transfectants expressing human
endoglin, whereas platelets from Glanzmann's
thrombasthenia patients lacking the αIIbβ3
integrin are defective for
endoglin-dependent adhesion to endothelial cells. Furthermore, the bleeding time, but not the prothrombin time, is significantly prolonged in
endoglin-haplodeficient (Eng +/-) mice compared to Eng +/+ animals. These results suggest a new role for
endoglin in αIIbβ3
integrin-mediated adhesion of platelets to the endothelium, and may provide a better understanding on the basic cellular mechanisms involved in hemostasis and thrombo-inflammatory events.