Abnormal Responses of Myeloid Progenitor Cells to Recombinant Human Colony-Stimulating Factors in Congenital Neutropenia

• Published in: Blood Vol. 75; no. 11; pp. 2143 - 2149
• Main Authors: Kobayashi, Masao, Yumiba, Chimako, Kawaguchi, Yoshinori, Tanaka, Yoshito, Ueda, Kazuhiro, Komazawa, Yoshitaka, Okada, Kohsuke
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.06.1990; The Americain Society of Hematology
• Subjects: Agranulocytosis - congenital; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Bone Marrow - drug effects; Bone Marrow - pathology; Cell Count - drug effects; Child, Preschool; Colony-Stimulating Factors - pharmacology; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Hematopoiesis - drug effects; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - pathology; Hematopoietic Stem Cells - physiology; Humans; Interleukin-3 - pharmacology; Male; Medical sciences; Neutropenia - congenital; Neutropenia - pathology; Neutrophils - drug effects; Pharmacology. Drug treatments; Recombinant Proteins - pharmacology; Human; Congenital; Cytokine; Infant; Hemopathy; In vitro; In vivo; Granulocyte colony stimulating factor; Treatment; Interleukin 3; Bone marrow; CFU-C-Cell; Child; Granulopoiesis; Neutropenia
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V75.11.2143.2143

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 μg/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.