Hematologic effects of stem cell factor alone and in combination with G-CSF and GM-CSF in vivo and in vitro in rodents.
The intravenous injection of rrSCF causes neutrophilia and lymphocytosis as well as the appearance of immature myeloid cells and occasional blast cells in the circulation. The marrow shows a left-shifted myeloid and erythroid hyperplasia as evidenced by increases in numbers of morphologically recognizable early myeloid and erythroid precursors. A decrease in the number of mature marrow neutrophils is noted, suggesting that the release of marrow neutrophils contributes to the peripheral neutrophilia. After 2 weeks of daily injections of rrSCF, the marrow demonstrates a remarkable mast cell hyperplasia accompanied by erythroid and lymphoid hypoplasia. rrSCF causes mast cells to appear in the circulation and causes a systemic increase in embryonic connective tissue-type mast cells. In vitro long-term culture of mouse marrow cells with rrSCF results in an outgrowth of mast cells. The coinjection of rrSCF and G-CSF for 1 week causes a synergistic increase in mature marrow neutrophils accompanied by a striking decrease in erythroid and lymphoid marrow elements. Spleens demonstrate increased granulopoiesis as well as erythropoiesis as compared to the spleens of rats treated with single growth factors. Splenic extramedullary erythropoiesis may act to compensate for the decrease in marrow erythropoiesis. The coinjection of rrSCF and G-CSF causes an increase in marrow mast cells at the end of 1 week, but the increase is much less than in rats treated with rrSCF alone. The combination of rrSCF and G-CSF causes a synergistic peripheral neutrophilia. In vivo daily administration of SCF plus GM-CSF results in a synergistic increase in marrow neutrophils, but not the striking synergistic increase in circulating neutrophils that is observed after SCF plus G-CSF. Colony-forming assays reveal a synergistic increase in CFU-GMs in the marrow, but not in peripheral blood, after coincubation with SCF plus GM-CSF as opposed to GM-CSF alone, demonstrating anatomic compartmentalization between a more primitive marrow CFU-GM subset and a more mature peripheral blood CFU-GM subset.
Ulich
T R
TR
Department of Pathology, University of California San Diego Medical Center 92103.
Yi
E S
ES
Yin
S
S
del Castillo
J
J
McNiece
I
I
Yung
Y P
YP
Zsebo
K M
KM
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D011993:Recombinant Fusion Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor