Recombinant human granulocyte-macrophage colony-stimulating factor promotes megakaryocyte maturation in nonhuman primates.
Megakaryocytes are responsive to several nonlineage-specific cytokines in vitro. In this study, we examined the in vivo effects of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) on late stages of megakaryocytopoiesis in the rhesus monkey. Four rhesus monkeys were given 10 micrograms/kg body weight/day of rh GM-CSF s.c. in two divided doses daily for 8 days. Megakaryocyte maturation was evaluated serially by measuring nuclear ploidy and cytoplasmic size. GM-CSF-treated monkeys developed significant shifts in ploidy distribution from days 3 through 15 (p less than or equal to 0.001), with increased frequencies of 64N and 128N megakaryocytes. Mean megakaryocyte size increased 92.5% on day 9, paralleling the increase in DNA content, although megakaryocyte size within ploidy groups did not increase. Megakaryocyte number remained unchanged following rh GM-CSF treatment. The platelet count responses were variable, and mean platelet volume did not change. The present study demonstrates that therapeutic doses of rh GM-CSF stimulate megakaryocyte endomitosis and increase mean size. The data indicate that GM-CSF is effective in promoting the maturation stage of megakaryocyte development but does not result in a consistent thrombopoietic response.
Stahl
C P
CP
Division of Immunologic, Oncologic, and Hematologic Diseases, Centers for Disease Control, U.S. Department of Health and Human Services, Atlanta, GA 30333.
Winton
E F
EF
Monroe
M C
MC
Holman
R C
RC
Zelasky
M
M
Liehl
E
E
Myers
L A
LA
McClure
H
H
Anderson
D
D
Evatt
B L
BL
D000818:Animals; D001854:Bone Marrow Cells; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006400:Hematocrit; D006410:Hematopoiesis / Q000187:drug effects*; D007958:Leukocyte Count / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D008533:Megakaryocytes / Q000166:cytology*; D011003:Ploidies; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor