Possible role of stem cell factor as a serum factor: monoclonal anti-c-kit antibody abrogates interleukin-6-dependent colony growth in serum-containing culture.
The monoclonal rat anti-c-kit antibody (ACK2), which abrogates colony growth supported by stem cell factor (SCF), significantly inhibited the interleukin-6 (IL-6)-dependent growth of hematopoietic progenitors derived from spleen cells of normal and 5-fluorouracil (5-FU)-treated mice and from bone marrow cells of normal mice in serum-containing culture. The numbers and types of colonies supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), however, were not influenced by the addition of ACK2 to the cultures of the bone marrow cells from normal mice. In replating experiments with pooled blast cells, ACK2 caused a partial, but significant, inhibition of GM colony growth supported by a combination of IL-6 and fetal bovine serum (FBS), which suggests that FBS is one source of the SCF activity. Conversely, the addition of SCF or FBS with IL-6 to a serum-free culture had significant synergistic effects on the total number of colonies derived from post-5-FU spleen cells and from pooled blast cells. The dose response study showed that the ability of 30% FBS to interact with IL-6 on the colony growth by post-5-FU spleen cells was equivalent to that of approximately 5 ng/mL SCF. These findings suggest that c-kit plays an important role in the growth of hematopoietic progenitors responding to IL-6, and that SCF in the serum affects the development of hematopoietic progenitors in serum-containing cultures.
Shiohara
M
M
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Koike
K
K
Kubo
T
T
Amano
Y
Y
Takagi
M
M
Muraoka
K
K
Nakao
J
J
Nakahata
T
T
Komiyama
A
A
D000818:Animals; D000911:Antibodies, Monoclonal; D001769:Blood; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood; D005472:Fluorouracil / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D051381:Rats; D013154:Spleen / Q000166:cytology; D019089:Stem Cell Factor
D000911:Antibodies, Monoclonal; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D005472:Fluorouracil