Long-term recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment severely depresses murine marrow erythropoiesis without causing an anemia.
We hereby report profound effects of long-term granulocyte colony-stimulating factor (G-CSF) administration on murine erythropoiesis. Recombinant human (rh)G-CSF (150 micrograms/kg body weight/day) was administered over 24 days to female C57Bl mice. Marrow erythroid colony-forming units (CFU-E) and erythroblast numbers declined to less than 5% of normal, whereas splenic erythropoiesis simultaneously increased. Splenic erythropoiesis effectively compensated for the loss of marrow erythropoiesis as indicated by the maintenance of a normal hematocrit. In the marrow the numbers of spleen colony-forming units (CFU-S) and erythroid burst-forming units (BFU-E) declined as well. Simultaneously, however, these numbers increased both in the spleen and in the peripheral blood by a factor of 20 to 30. These findings suggest a continuous migration of stem cells and progenitor cells out of the marrow and an efficient seeding in the spleen, directly or indirectly induced by G-CSF. In addition the differentiation and/or amplification of BFU-E to CFU-E was impaired in the marrow but not in the spleen. The marrow and splenic microenvironment also behaved differently with respect to granulopoiesis. G-CSF did not lead to an enhanced granuloid amplification in the spleen but exerted its proliferation activity mainly in the marrow. These findings imply that prolonged G-CSF treatment might cause erythroid depression in animals and humans when spleen erythropoiesis is less efficient than in mice.
de Haan
G
G
Laboratory of Physiological Chemistry, University of Groningen, The Netherlands.
Loeffler
M
M
Nijhof
W
W
D000740:Anemia / Q000139:chemically induced; D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D001854:Bone Marrow Cells; D002452:Cell Count / Q000187:drug effects; D004900:Erythroblasts / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000187:drug effects; D013997:Time Factors
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor