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PMID:1350248
| Citation |
Okada, S, Nakauchi, H, Nagayoshi, K, Nakamura, M, Miura, Y and Suda, T (1992) Synergistic effect of IL-3 and IL-6 on highly enriched murine hemopoietic progenitors. Exp. Hematol. 20:546-51 |
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| Abstract |
It has been reported that interleukin 6 (IL-6) acts on hemopoietic stem cells in synergism with interleukin 3 (IL-3), but it has not yet been clarified whether IL-6 acts directly on the stem cells or not. To investigate the mechanism of the synergism between IL-3 and IL-6, we sorted hemopoietic stem cells from untreated murine bone marrow cells using a two-laser fluorescence-activated cell sorter (FACS). Cells negative for the lymphohemopoietic lineage (lineage-negative, Lin-), with a high affinity to wheat germ agglutinin (WGA+), and showing a low expression of Thy-1 antigen (Thy-1low) were sorted and analyzed by in vitro and in vivo colony formation. This fraction was 0.4% of the total mononuclear bone marrow cells. Approximately 25% of these Lin-WGA+Thy-1low cells showed in vitro colony formation, whereas approximately 1% of them formed day-8 and day-12 spleen colonies. Thus, it appears that the Lin-WGA+Thy-1low cells were a highly enriched stem cell population. By FACS clone sorting, single cells were isolated from the enriched stem cell fraction and cultured in semisolid or liquid culture systems. Addition of IL-6 to methylcellulose medium containing IL-3 did not significantly increase the number of colonies. It is thus suggested that the target cells of IL-3 and IL-6 are the same as those of IL-3. The secondary colony-forming ability of primary colonies that developed in the presence of IL-6 and IL-3 was higher than that of colonies formed in the presence of IL-3 alone. In correspondence with this finding, the numbers of myeloid colonies and spleen colony-forming units (CFU-S) were increased by the incubation of these sorted cells for 7 days with IL-6 and IL-3 when compared with the effect of IL-3 alone. Therefore, it is concluded that IL-6 acts directly on hemopoietic stem cells to enhance their proliferation. |
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| Keywords |
Animals; Antigens, Surface/analysis; Antigens, Thy-1; Bone Marrow/drug effects; Bone Marrow/immunology; Bone Marrow Cells; Cell Division/drug effects; Cell Separation; Drug Synergism; Flow Cytometry; Hematopoietic Stem Cells/cytology; Hematopoietic Stem Cells/drug effects; Interleukin-3/pharmacology; Interleukin-6/pharmacology; Membrane Glycoproteins/analysis; Mice; Mice, Inbred Strains; Wheat Germ Agglutinins/analysis |
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