Summary
Thrombopoietin (Mpl ligand), interleukin-6 (IL-6), and interleukin-11 (IL-11) differ
in their effects on megakaryocyte maturation and development. In the present study,
the impact of these thrombocytopoietic cytokines on biochemical and structural granule
and membrane components was examined. Western blotting was performed on equivalent
amounts of isolated megakaryocyte or platelet protein and the relative intensities
of the enhanced chemiluminescent-visualized bands were quantitated by densitometry.
Megakaryocyte growth and development factor (MGDF), a recombinant thrombopoietin-related
molecule, significantly increased megakaryocyte fibronectin (72%), thrombospondin
(55%), von Willebrand factor (28%) and p-selectin (CD62p) (37%) when compared 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 mature-appearing megakaryocytes. Platelets from
MGDF-treated mice showed small increases in fibronectin (8%), and CD62p (18%), but
did not show increases in other measured α-granule proteins. Neither IL-6 nor IL-11
increased megakaryocyte or platelet α-granule proteins over levels observed in saline
controls. IL-11 treated megakaryocytes, while also exhibiting an increase in ribosomes,
were characterized by prominent cytoplasmic fragmentation. The study demonstrates
the impact of Mpl ligand in increasing synthesized megakaryocyte α-granule proteins
and of IL-11 in promoting megakaryocyte fragmentation.