A role of GAGs in ECM on morphogenesis of megakaryocytes.

The morphogenesis of megakaryocytes that results in the formation of cytoplasmic processes is thought to be the final maturation step before liberation of platelets. We studied the in vitro effects of glycosaminoglycans (GAGs) which are abundant in the bone marrow extracellular matrices, on the morphogenesis of murine megakaryocytes and compared them with those of thrombopoietic cytokines. Heparin, heparan sulfate, chondroitin-6 sulfate, and dermatan sulfate promoted the formation of megakaryocytic processes. Hyaluronic acid failed to support this phenomenon, suggesting that sulfated GAGs in extracellular matrices are involved in the morphogenesis of megakaryocytes. Sulfated GAGs began to act on megakaryocytes with a higher ploidy (16N-32N) from 6 to 24h after incubation, whereas neither rhIL-6 nor rhIL-11 affected this early phase. Our findings indicate that sulfated GAGs promote the morphogenesis of murine megakaryocytes and participate in thrombopoiesis in a different manner from that of cytokines such as rhlL-6 and rhIL-11. IL-I1.