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Effect of thrombopoietin on the development of megakaryocytes and
platelets: an ultrastructural analysis
D Zucker-Franklin and K Kaushansky
New York University Medical Center, New York 10016, USA.
Megakaryocytopoiesis and platelet production can be assessed with
reasonable accuracy by quantitative and functional analyses of circulating
platelets. The evaluation of megakaryocytopoiesis in culture has remained
unsatisfactory, particularly because platelet production is rarely
observed. In mouse culture systems, megakaryocytes have been identified
almost entirely by measurements of acetyl cholinesterase, size, and ploidy
without concomitant assessment of maturation based on such criteria as the
formation of granules, demarcation membranes, and cytoplasmic
fragmentation. The availability of various thrombopoietic cytokines, in
particular thrombopoietin (TPO), and their imminent clinical use has made a
more detailed understanding of their effect on differentiation and
maturation of the MK lineage more urgent. Therefore, ultrastructural
analyses were performed on megakaryocyte-depleted serum-free mouse bone
marrow cultures in the presence of TPO alone, TPO plus other cytokines, or
under conditions in which TPO and/or other cytokines were blocked with
neutralizing agents. These studies show that, while cytokines that use the
gp130 receptor subunit may function synergistically with TPO, in the
absence of TPO, such cultures do not yield morphologically recognizable MK.
On the other hand, TPO alone is able to drive MK to full maturation as
evidenced by the generation of granules, demarcation membranes, and
cytoplasmic fragmentation into platelets.
Volume 88,
Issue 5,
pp. 1632-1638,
09/01/1996
Copyright © 1996 by The American Society of Hematology
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