Interferon-gamma and interleukin-4 reciprocally regulate the production of monocytes/macrophages and neutrophils through a direct effect on committed monopotential bone marrow progenitor cells.
We studied the direct effects of interferon-gamma (IFN-gamma) in single cell colony assays of CD34+HLA-DR++ bone marrow progenitor cells stimulated by either granulocyte-colony-stimulating factor (G-CSF), interleukin(IL)-3, granulocyte/macrophage-colony-stimulating factor (GM-CSF), combinations of these CSF or medium conditioned by the 5637 human bladder carcinoma cell line. In this culture system IFN-gamma stimulated monocytic colonies (CFU-M) no matter which CSF or CSF combination was used to support them and inhibited granulocytic colonies (CFU-G) if they were generated in the presence of G-CSF. IL-4 antagonized the myelopoietic effects of IFN-gamma: the IFN-gamma-induced suppression of G-CSF-supported CFU-G, as well as the stimulation of CFU-M, were reversed by IL-4. In all cultures, IFN-gamma had a limited, but statistically non-significant, inhibitory effect on CFU-GM, which was not affected by the presence of IL-4. These data show that IFN-gamma and IL-4 reciprocally regulate the generation of myeloid cells involved in humoral (neutrophils) and cellular (macrophages) immune responses through a direct effect on monopotential myeloid progenitor cells.
Snoeck
H W
HW
Laboratory of Experimental Hematology, University of Antwerp (UZA), Edegem, Belgium.
Lardon
F
F
Lenjou
M
M
Nys
G
G
Van Bockstaele
D R
DR
Peetermans
M E
ME
D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits
D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D007371:Interferon-gamma