Interleukin-12 enhances interleukin-3 dependent multilineage hematopoietic colony formation stimulated by interleukin-11 or steel factor.
Interleukin 12 (IL-12: natural killer cell stimulatory factor, NKSF; cytotoxic lymphocyte maturation factor, CLMF) was studied for its effect on colony formation and lineage expression of low-density bone marrow cells from 5-fluorouracil-treated mice, and of sorted stem cells using a semi-solid culture assay in the absence or presence of IL-3, IL-11, Steel factor (SF) and erythropoietin. IL-12 did not support colony formation as a single factor, nor in the presence of IL-11 or SF. In IL-3-containing cultures, IL-12 slightly enhanced neutrophilic and monocyte differentiation. Both SF and IL-11 synergized with IL-3 to increase the percentage of multilineage colonies and the number of colonies containing erythrocytes, megakaryocytes, neutrophils, eosinophils, monocytes/macrophages, and blast cells, but not mast cells. In the presence of IL-3 + IL-11, IL-12 greatly enhanced neutrophil, megakaryocyte, erythrocyte, and mast cell development. In IL-3 + SF-containing cultures, IL-12 further increased colony numbers and a higher percentage of colonies expressed neutrophilic, megakaryocytic, erythroid, monocytic, blast cell, and/or mast cell lineages. Colony size and the presence of eosinophils in colonies were unaffected by IL-12 addition. These effects of IL-12 could not be reversed by antibodies against interferon-gamma. Our data show that IL-12 may act as a synergistic factor, stimulating multilineage expression of hemopoietic stem cells, probably via a direct action. The observed activity of IL-12, however, required the presence of a least two factors, i.e. either IL-3 + IL-11, or IL-3 + SF.
Ploemacher
R E
RE
Institute of Hematology, Erasmus University, Rotterdam, The Netherlands.
van Soest
P L
PL
Boudewijn
A
A
Neben
S
S
D000818:Animals; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D004912:Erythrocytes / Q000166:cytology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017370:Interleukin-11 / Q000494:pharmacology*; D018664:Interleukin-12; D007377:Interleukin-3 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009000:Monocytes / Q000166:cytology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D017370:Interleukin-11; D007377:Interleukin-3; D007378:Interleukins; D019089:Stem Cell Factor; D018664:Interleukin-12