POSSIBLE ROLE OF STEM-CELL FACTOR AS A SERUM FACTOR - MONOCLONAL ANTI-C-KIT ANTIBODY ABROGATES INTERLEUKIN-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 th e interleukin-6 (IL-6)-dependent growth of hematopoietic progenitors d erived from spleen cells of normal and 5-fluorouracil (5-FU)-treated m ice and from bone marrow cells of normal mice in serum-containing cult ure. The numbers and types of colonies supported by IL-3, granulocyte- macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-s timulating factor (G-CSF), however, were not influenced by the additio n of ACK2 to the cultures of the bone marrow cells from normal mice. I n replating experiments with pooled blast cells, ACK2 caused a partial , but significant, inhibition of GM colony growth supported by a combi nation of IL-6 and fetal bovine serum (FBS), which suggests that FBS i s one source of the SCF activity. Conversely, the addition of SCF or F BS with IL-6 to a serum-free culture had significant synergistic effec ts 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 grow th of hematopoietic progenitors responding to IL-6, and that SCF in th e serum affects the development of hematopoietic progenitors in serum- containing cultures.