The effects of Mpl-ligand, interleukin-6 and interleukin-11 on megakaryocyte and platelet alpha-granule proteins

Thrombopoietin (Mpl ligand), interleukin-6 (IL-6), and interleukin-ll (IL-l l) differ in their effects on megakaryocyte maturation and development. In the present study, the impact of these thrombocytopoietic cytokines on bioc hemical and structural granule and membrane components was examined. Wester n blotting was performed on equivalent amounts of isolated megakaryocyte or platelet protein and the relative intensities of the enhanced chemilumines cent-visualized bands were quantitated by densitometry. Megakaryocyte growt h and development factor (MGDF), a recombinant thrombopoietin-related molec ule, significantly increased megakaryocyte fibronectin (72%), thrombospondi n (55%), von Willebrand factor (28%) and p-selectin (CD62p) (37%) when comp ared to equivalent amounts of protein from saline-treated controls (p<0.01) . Megakaryocyte fibrinogen was not increased. Ultrastructurally, there was a marked increase in ribosomes and rough endoplasmic reticulum even in matu re-appearing megakaryocytes. Platelets from MGDF-treated mice showed small increases in fibronectin (8%), and CD62p (18%), but did not show increases in other measured alpha-granule proteins. Neither IL-6 nor IL-ll increased megakaryocyte or platelet alpha-granule proteins over levels observed in sa line controls. IL-11 treated megakaryocytes, while also exhibiting an incre ase in ribosomes, were characterized by prominent cytoplasmic fragmentation . The study demonstrates the impact of Mpl ligand in increasing synthesized megakaryocyte alpha-granule proteins and of IL-11 in promoting megakaryocy te fragmentation.