Abnormal responses of myeloid progenitor cells to recombinant human colony-stimulating factors in congenital neutropenia.
The effects of recombinant human interleukin-3 (IL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) on the growth of myeloid progenitor cells (CFU-C) in semisolid agar culture were studied in two patients with Kostmann-type congenital neutropenia. CFU-C growth in bone marrow cells from patients was significantly reduced in response to various concentrations of either IL-3 or G-CSF alone, compared with that from normal subjects. There was no inhibitory effect of bone marrow cells from patients on normal CFU-C formation supported by IL-3 or G-CSF. However, the simultaneous stimulation with IL-3 and G-CSF induced the increase of CFU-C formation in patients with congenital neutropenia. Furthermore, CFU-C growth in both patients was supported when bone marrow cells were preincubated with IL-3 in liquid culture followed by the stimulation with G-CSF in semisolid agar culture. In contrast, that was not supported by the preincubation with G-CSF and the subsequent stimulation with IL-3. This evidence suggests that the hematopoietic progenitor cells in patients with congenital neutropenia have the potential for developing CFU-C in the combined stimulation with IL-3 and G-CSF, and that this growth may be dependent on the priming of IL-3 followed by the stimulation with G-CSF. The level of mature neutrophils in peripheral blood was not fully restored to normal levels by the daily administration of G-CSF in doses of 100 to 200 micrograms/m2 of body surface area for 20 to 25 days in both patients. These observations raise the possibility that the combination of IL-3 and G-CSF might have a potential role for the increase of neutrophil counts in patients with congenital neutropenia.
Department of Pediatrics, Hiroshima University School of Medicine, Japan.
M
M
Kobayashi
C
C
Yumiba
Y
Y
Kawaguchi
Y
Y
Tanaka
K
K
Ueda
Y
Y
Komazawa
K
K
Okada
D000380:Agranulocytosis / Q000151:congenital*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002452:Cell Count / Q000187:drug effects; D002675:Child, Preschool; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D008297:Male; D009503:Neutropenia / Q000151:congenital* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor