Synergistic effect of IL-3 and IL-6 on highly enriched murine hemopoietic progenitors

S. Okada, H. Nakauchi, K. Nagayoshi, M. Nakamura, Y. Miura, T. Suda

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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-1(low)) 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-1(low) 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+Thy1(low) 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.

Original languageEnglish
Pages (from-to)546-551
Number of pages6
JournalExperimental Hematology
Volume20
Issue number5
Publication statusPublished - 1992 Jan 1

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Keywords

  • enriched hemopoietic cells
  • interleukin 3
  • interleukin 6

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

Cite this

Okada, S., Nakauchi, H., Nagayoshi, K., Nakamura, M., Miura, Y., & Suda, T. (1992). Synergistic effect of IL-3 and IL-6 on highly enriched murine hemopoietic progenitors. Experimental Hematology, 20(5), 546-551.