Transient thrombocytopenia produced by administration of macrophage colony-stimulating factor: investigations of the mechanism.
Administration of macrophage colony-stimulating factor (M-CSF) to mice (2 to 8 mg/kg/d x 5d) produced dose-dependent thrombocytopenia, which reached its nadir on days 4 to 5, followed by rapid recovery. Surprisingly, when administration of M-CSF was prolonged, the thrombocytopenia completely resolved, despite continued treatment. Splenectomy did not prevent the thrombocytopenia. Readministration of M-CSF after various intervals continued to produce the thrombocytopenic effect, even after 35 days. Measurements of Meg-CFC and megakaryocyte ploidy during the periods of M-CSF treatment and recovery of normal platelet levels showed no evidence of bone marrow suppression. Platelet survival was markedly decreased after 5 days of M-CSF (at the platelet count nadir) and after 9 days of continued M-CSF treatment, when the platelet count had returned to normal. Platelets from M-CSF-treated donors demonstrated normal survival when transfused into normal recipients. We concluded that thrombocytopenia produced by M-CSF was not due to suppression of thrombopoiesis, but to increased activity of the monocyte/macrophage system, which caused shortened platelet survival, and that subsequently, increased platelet production compensated for ongoing platelet destruction and resulted in normal platelet levels.
Baker
G R
GR
Department of Laboratory Medicine, University of California School of Medicine, San Francisco, CA, USA.
Levin
J
J
D000222:Adaptation, Physiological; D000818:Animals; D001792:Blood Platelets / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006410:Hematopoiesis; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008533:Megakaryocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013156:Splenectomy; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor