Extracellular matrix receptors and the differentiation of human megakaryocytes in vitro

We investigated the expression and functions of extracellular matrix recept ors (or integrins) in the course of the differentiation of human megakaryoc ytes (Mks) leading to the formation of platelets. Integrins beta 1 or Very Late Antigens (VLA) are specialized transmembrane receptors allowing the at tachment of the cells to collagen (VLA-2), fibronectin (VLA-4 and -5) and l aminin (VLA-6). A proportion of committed megakaryocytic progenitor cells ( CFU-MK) adhere to fibronectin but not to collagen or laminin. The early imm ature Mks are retained on fibronectin (30%) and laminin (12%) but not on co llagen whereas large mature Mks are still adherent to fibronectin and lamin in and also acquired the capacity to adhere to collagen, The expression of the different VLA in the maturation of Mks correlates well with their adhes ive properties. Hence, VLA-2 is not expressed on immature Mks but is presen t on the mature polyploid cells. VLA-4 is detected only on immature Mks whi ch do not seem to bear VLA-5, while this last integrin appears on late Mks. VLA-6 showed a broad distribution from the early to late stages of Mks dif ferentiation. Integrins beta 3 of the cytoadhesin family are represented by alpha IIb bet a 3 that is the receptor for fibrinogen and alpha V beta 3 which mediates a dhesion to vitronectin. alpha IIb beta 3 is present on the CFU-MK and highl y expressed throughout the Mks maturation stages while alpha V beta 3 expre ssion is much lower and seems to be detected only on the late Mks. The regu lation of the expression of these receptors by cytokines and their respecti ve roles in the maturation of Mks and the final production of platelets, ar e discussed. The development of efficient culture systems of human Mks in t he presence of the recently cloned thrombopoietin will undoubtly help to sh ed more light on the molecular mechanisms of their interactions via integri ns with the BM microenvironment.