Hematologic effects of stem cell factor in vivo and in vitro in rodents.
Recombinant rat stem cell factor (rrSCF) administered to rats as a single intravenous injection causes a dose-dependent neutrophilia and lymphocytosis as well as the appearance of immature myeloid cells and occasional blast cells in the circulation. Neutrophilia begins at 2 hours, peaks at 4 to 6 hours, and subsides between 12 and 24 hours. Lymphocytosis occurs at 0.5 hours and has subsided by 2 hours. rrSCF-induced neutrophilia and lymphocytosis are abrogated by boiling, demonstrating that endotoxin-contamination of the rrSCF preparation is not responsible for the observed hematologic effects. The bone marrow at 6 hours after injection of rrSCF shows a left-shifted myeloid and erythroid hyperplasia as evidenced by significant increases in the absolute numbers of morphologically recognizable early myeloid and erythroid precursors. A concurrent decrease in the absolute numbers 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, bone marrow smears demonstrate a remarkable mast cell hyperplasia accompanied by a decrease in total marrow cellularity and by a striking erythroid and lymphoid hypoplasia. rrSCF also causes mast cells to appear in the circulation and causes a systemic increase in embryonic connective tissue-type, but not mucosal-type, mast cells. In vitro long-term culture of lineage-depleted mouse bone marrow cells with rrSCF results in an almost pure outgrowth of mast cells.
Ulich
T R
TR
Department of Pathology, University of California Irvine Medical School 92717.
del Castillo
J
J
Yi
E S
ES
Yin
S
S
McNiece
I
I
Yung
Y P
YP
Zsebo
K M
KM
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D016298:Hematopoietic Cell Growth Factors / Q000633:toxicity*; D006965:Hyperplasia; D007700:Kinetics; D007964:Leukocytosis / Q000139:chemically induced* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000633:toxicity; D019089:Stem Cell Factor; D014132:Trachea / Q000187:drug effects / Q000473:pathology
D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D019089:Stem Cell Factor