Actions of Human Interleukin-4/B-Cell Stimulatory Factor-1 on Proliferation and Differentiation of Enriched Hematopoietic Progenitor Cells in Culture

• Published in: Blood 1990-04, Vol.75 (8), p.1615-1621
• Main Authors: Sonoda, Yoshiaki, Okuda, Tsukasa, Yokota, Shouhei, Maekawa, Taira, Shizumi, Yukari, Nishigaki, Hikari, Misawa, Shinichi, Fujii, Hiroshi, Abe, Tatsuo
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow Cells; Cell Differentiation - drug effects; Cell Division - drug effects; Cell physiology; Cells, Cultured; Colony-Stimulating Factors - pharmacology; Dose-Response Relationship, Drug; Erythroid Precursor Cells - drug effects; Erythropoietin - pharmacology; Fundamental and applied biological sciences. Psychology; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells - drug effects; Humans; Interleukin-4 - pharmacology; Molecular and cellular biology; Neutrophils - cytology; Neutrophils - drug effects; Responses to growth factors, tumor promotors, other factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V75.8.1615.1615

We studied the effects of recombinant human interleukin-4 (IL-4) on colony formation by enriched hematopoietic progenitors. IL-4 alone did not support colony formation at all. When IL-4 was combined with granulocyte colony-stimulating factor (G-CSF), the number of pure neutrophil colonies increased three times over that supported by G-CSF alone. IL-4 added 5 days after the addition of G-CSF failed to exert this synergistic effect, indicating that IL-4 acts on the early stage of proliferation. The mapping experiments (sequential observation of colony formation) have clearly shown that IL-4 did not initiate progenitor cell proliferation. Based on these data, IL-4 may possess a direct action on progenitor cells; however, it can only act as a costimulant with G-CSF. In contrast, IL-4 had possible inhibitory effects on macrophage colony formation supported by interleukin-3 (IL-3) and macrophage colony-stimulating factor (M-CSF). In other words, IL-4 may induce progenitor cells to become sensitive to G-CSF and thereby induce neutrophil differentiation. Delayed addition experiments demonstrated that human IL-4, unlike murine IL-4, could support neither proliferation nor survival of erythroid burst or mixed colony forming cells. Neutrophil colony forming cells only survived and recovered after addition of G-CSF and erythropoietin on day 5 of incubation. On the other hand, IL-3 supported neutrophil, erythroid burst, and mixed colony forming cells as reported previously (Sonoda et al, Proc Natl Acad Sci USA, 85:4360, 1988). These results led us to propose that IL-4 possibly acts with more mature progenitor cells than those of IL-3 or granulocyte-macrophage (GM)-CSF.