Effects of monocyte-macrophage colony-stimulating factor (M-CSF) on in vitro erythropoiesis of marrow progenitor cells from patients with renal anemia.
We examined the influence of monocyte-macrophage colony-stimulating factor (M-CSF) on erythropoiesis both in vitro and in vivo in 98 patients with chronic renal failure who were undergoing hemodialysis. Serum levels of M-CSF and the clinical response to therapy with human recombinant erythropoietin (Epo) were analyzed. The following results were obtained: 1) The serum level of M-CSF was 6.90 +/- 2.41 ng/ml in the patient population (n = 98), but only 2.0 +/- 0.3 ng/ml in 10 healthy donors. 2) 41 of the 98 anemic patients were treated with various doses of Epo for 3 months, and the average increase in the blood hemoglobin level during this period was 26.1 +/- 12.5 mg/dl/unit of Epo/kg patient's b.w./week. Lower levels of M-CSF before treatment significantly predicted a better response to subsequent Epo therapy (r = -0.496, p < 0.001). 3) When cultured with a maximally stimulatory amount of Epo (10 IU/ml), the number of marrow early erythroid progenitor cells (burst-forming unit for erythroid, BFU-E) in patients was identical to that in normal donors, while the number of late progenitors (colony-forming unit for erythroid, CFU-E) was relatively lower in patients. 4) The addition of recombinant M-CSF to the culture resulted in suppression of erythroid progenitor cell growth in the patient population, but induced enhancement in normal donors. The inhibitory effect of M-CSF on the patients' cells was not eliminated by the addition of antibodies against interleukin-1 alpha/beta, tumor necrosis factor-alpha, or interferon-alpha/beta/gamma. Supernatants from marrow mononuclear cells cultured in the presence of M-CSF carried this inhibitory effect on marrow CD34+ cells obtained from patients. Together, these results suggest that M-CSF aggravates a previously existing decreased sensitivity of erythroid progenitor cells to Epo in some patients with renal anemia.
Kawano
Y
Y
Department of Pediatrics, University of Tokushima, Japan.
Takaue
Y
Y
Minakuchi
J
J
Kawashima
S
S
Kimura
F
F
Motoyoshi
K
K
Abe
T
T
Sato
J
J
Hirao
A
A
Saito
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood* / Q000628:therapy; D016022:Case-Control Studies; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000502:physiology*; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood / Q000494:pharmacology*; D008875:Middle Aged
D004921:Erythropoietin; D016173:Macrophage Colony-Stimulating Factor