Platelet membrane glycoproteins: historical perspectives.

Abstract

3–9. The function of blood platelets to prevent blood loss at injured sites in the vasculature depends largely on their capacity to adhere, aggregate, promote coagulation and secrete factors that induce vasoconstriction and recruit inflammatory cells. Produced in large numbers from megakaryocytes, platelets enter the circulation for 7–10 days primed to fulfill their hemostatic function. By 1970, thoughts were becoming well formulated concerning the involvement of platelets not only in hemostasis, but also in the pathogenesis of arterial thrombosis. By this timeframe, pioneering studies had also established many of the basic concepts of platelet biology. Physiologic agonists of platelet aggregation such as ADP, collagen and thrombin had already been identified. Protein cofactors including von Willebrand factor (VWF) and fibrinogen were known to be involved in platelet aggregation [1]. However, in the background of these basic studies, the elegant morphological characterizations of platelets by investigators such as Jim White and Dorothea Zucker-Franklin were teaching us that that the two primary activities of platelets in thrombosis and hemostasis, that is adhesion and aggregation, were dependent upon as yet undescribed elements on the platelet membrane surface. It was also clear that this surface had procoagulant activity. While important studies had been initiated to study platelet membrane proteins, for example, the work in Graham Jamieson’s laboratory to characterize peptide fragments of membrane proteins released by proteases [2–5], and the contributions of Ralph Nachman’s laboratory on platelet membrane protein content [6,7], further progress in our understanding of thrombosis and hemostasis required defining the protein content of the platelet membrane surface and identifying specific proteins that were involved in platelet function. What follows is a story of collaborative research that began 30 years ago and has lasted across our careers. The ability to label platelet surface glycoproteins with radioisotopes and to solubilize them in sodium dodecyl sulfate (SDS) and separate them by polyacrylamide gel electrophoresis (PAGE) was an important advance that provided the basis for each of our projects. Using these techniques, each of us began with different perspectives and different goals. Our ideas all came together in 1975 at the meeting of the International Society for Thrombosis and Haemostasis (ISTH) in Paris. By that time we appreciated the complexity of the platelet membrane glycoproteins and understood that they had important roles in platelet function, documented by their abnormalities in the congenital disorders, Glanzmann thrombasthenia and Bernard–Soulier syndrome. Many of the other early investigators in this field are to be found in Fig. 1, a group photograph taken at am eeting held in San Antonio, Texas in 1983 to develop our book, Platelet Membrane Glycoproteins (Fig. 2) [8]. But to tell the story of how the three of us arrived at this point requires that we begin again, each of us on our own.