1274 Characterization of Human Megakaryocytes

Platelets are blood elements that play a key role in coagulation and participate directly in the processes of thrombosis and atherosclerosis (1-3). However, the physiologic mechanisms governing platelet formation and release from megakaryocytes remain largely unknown (4). Platelets are nonnucleated cells with only a vestigial protein synthetic apparatus, and therefore most of the structural and functional components associated with platelets are believed to be derived from megakaryocytes. Thus, a better understanding of megakaryocyte biology should provide important new insights into the mechanisms of platelet production and into the expression of the various aspects of platelet function during thrombopoiesis. Since Wright first hypothesized the megakaryocyte-platelet relationship over 70 yr ago (5), most of the information concerning megakaryocytes has been obtained indirectly from studies of patients with platelet-associated bleeding disorders or experimental animals with artificially altered platelet levels (1, 6-8). Recently, techniques have been reported to obtain partially purified populations of megakaryocytes from mouse, rat, and guinea pig marrow tissue (9-11). With these preparations, various platelet-associated components have been identified in nonprimate megakaryocytes (12, 13). Moreover, culture systems have now been devised to grow and examine murine megakaryocytes in vitro (14, 15). In studies of the differentiation of other types of hematopoietic cells, cell component analysis has proven a valuable tool both for monitoring the degree of differentiation and for identifying the distinct types of progenitor cells (16-18). It is known that individual platelets are heterogenous in their density, size, and function (19, 20), but it has yet to be determined whether these diversities arise as a result of platelet formation occurring at different stages of megakaryocyte maturat ion or, alternatively, whether they arise because of the existence of separate and distinct committed progenitor cells that generate different platelet subsets. By analogy to other hemo-