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J. Exp. Med.,
Volume 187, Number 3, February 2, 1998 329-339
v
3 Integrin, and GPIb
By
From the Division of Hematology, University of Washington, Seattle, Washington 98195-7710
Although it has been reported that activated platelets can adhere to intact endothelium, the receptors involved have not been fully characterized. Also, it is not clear whether activated platelets bind primarily to matrix proteins at sites of endothelial cell denudation or directly to endothelial cells. Thus, this study was designed to further clarify the mechanisms of activated platelet adhesion to endothelium. Unstimulated human umbilical vein endothelial cell (HUVEC)
monolayers were incubated with washed, stained, and thrombin-activated human platelets. To
exclude matrix involvement, HUVEC were harvested mechanically and platelet binding was
measured by flow cytometry. Before the adhesion assay, platelets or HUVEC were treated with
different receptor antagonists. Whereas blockade of platelet 
1 integrins, GPIb
, GPIV, P-selectin,
and platelet-endothelial cell adhesion molecule (PECAM)-1 did not reduce platelet adhesion to
HUVEC, blockade of platelet GPIIbIIIa by antibodies or Arg-Gly-Asp (RGD) peptides markedly decreased adhesion. Moreover, when platelets were treated with blocking antibodies to
GPIIbIIIa-binding adhesive proteins, including fibrinogen and fibronectin, and von Willebrand factor (vWF), platelet binding was also reduced markedly. Addition of fibrinogen, fibronectin,
or vWF further increased platelet adhesion, indicating that both endogenous platelet-exposed and exogenous adhesive proteins can participate in the binding process. Evaluation of the HUVEC
receptors revealed predominant involvement of intercellular adhesion molecule (ICAM)-1 and
v3 integrin. Blockade of these two receptors by antibodies decreased platelet binding significantly. Also, there was evidence that a component of platelet adhesion was mediated by endothelial GPIb. Blockade of 1 integrins, E-selectin, P-selectin, PECAM-1, vascular cell adhesion molecule (VCAM)-1 and different matrix proteins on HUVEC did not affect platelet
adhesion. In conclusion, we show that activated platelet binding to HUVEC monolayers is
mediated by a GPIIbIIIa-dependent bridging mechanism involving platelet-bound adhesive proteins and the endothelial cell receptors ICAM-1, v3 integrin, and, to a lesser extent, GPIb.
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