Evidence suggesting a negative regulatory role for macrophages in murine erythropoiesis in vivo.
Increasing the rate of erythropoiesis in C57BL/6 mice, either by hypoxia or by the injection of recombinant erythropoietin (Epo), resulted in significant reductions in marrow macrophage number, as assessed by flow cytometry employing the monoclonal antibody against the macrophage antigen Mac-1 and by histologic determination of reductions in the number of marrow esterase-positive cells. This decline was paralleled by decreases in marrow colony-forming unit-macrophage (CFU-M) and colony-forming unit-granulocyte/macrophage (CFU-GM) number. The intramedullary concentration of the cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha), which are produced by macrophages, was also reduced. Cessation of erythropoiesis was associated with increases in macrophage number, CFU-M and CFU-GM colony number, and IL-1 alpha concentrations. Increased erythropoiesis resulted in reductions in number of burst-forming unit-erythroid (BFU-E) colonies, which were less sensitive to suppression by macrophages as evidence by less increase in colony number when macrophages were removed from the marrow before in vitro BFU-E culture. BFU-E colony number was suppressed less when IL-1 alpha and TNF-alpha were added to cultures obtained from animals with stimulated erythropoiesis. Compared to controls, BFU-E number and suppression by macrophages increased significantly when erythropoiesis was reduced. These observations provide compelling evidence for a regulatory role for macrophages in normal erythropoiesis in vivo, presumably acting as a negative balance to the stimulatory effects of Epo.
Wang
C Q
CQ
Geriatric Research Educational and Clinical Center (GRECC), John L. McClellan Memorial Veterans Hospital, Little Rock, AR 72205.
Udupa
K B
KB
Xiao
H
H
Lipschitz
D A
DA
D000818:Animals; D001854:Bone Marrow Cells; D004920:Erythropoiesis; D005260:Female; D000860:Hypoxia; D007375:Interleukin-1 / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha