Interactions among colony-stimulating factors, IL-1β, IL-6, and kit-ligand in the regulation of primitive murine hematopoietic cells Journal Article


Authors: Muench, M. O.; Schneider, J. G.; Moore, M. A. S.
Article Title: Interactions among colony-stimulating factors, IL-1β, IL-6, and kit-ligand in the regulation of primitive murine hematopoietic cells
Abstract: We have investigated the regulation of primitive murine hematopoietic progenitors by the cytokines interleukin 1 (IL-1), interleukin 6 (IL-6), and kit-ligand (KL). Individually these cytokines have a limited ability to stimulate the growth of high proliferative potential colony-forming cells (HPP-CFC) from 5-fluorouracil (5-FU)-purged bone marrow, but in combination these cytokines demonstrate synergism in promoting the growth of HPP-CFC. Furthermore, IL-1, IL-6, and KL, alone or in combination, synergized with the colony-stimulating factors (CSFs) granulocyte CSF (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), or interleukin 3 (IL-3) in clonal and liquid cultures of 5-FU-purged bone marrow. The pattern of HPP-CFC growth that was observed with 40 different cytokine combinations demonstrated the unique roles of IL-1, IL-6, and KL in the regulation of HPP-CFC proliferation. Short-term liquid cultures (Δ-cultures), with secondary recloning, of 5-FU-purged bone marrow were stimulated to greatly expand the numbers of progenitor cells generated in response to cytokine stimulation. The greatest expansion, over 1800-fold, of the more mature progenitor compartments took place in Δ-cultures stimulated with IL-1, IL-6, and KL plus IL-3. However, the combination of IL-1 and IL-6 plus KL was optimal in expanding HPP-CFC, increasing their numbers by 700-fold. The ability to expand early progenitor cells in Δ-cultures was further demonstrated by the > 100-fold expansions of day-12 spleen colony-forming units (CFU-S) by the synergistic interactions of IL-1 with IL-3 or KL.
Keywords: proto-oncogene proteins; fluorouracil; nonhuman; animal cell; mouse; animal; mice; animal tissue; cells, cultured; bone marrow; animal experiment; mice, inbred c57bl; drug synergism; cytokines; hematopoietic stem cells; interleukin 6; interleukin-6; hematopoiesis; granulocyte colony-stimulating factor; drug interactions; interleukin 1; interleukin-1; kit-ligand; granulocyte-macrophage colony-stimulating factor; interleukin 3; interleukin-3; colony stimulating factor; mice, inbred dba; macrophage colony-stimulating factor; male; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; colony forming unit s; cfu-s; proto-oncogene protein c-kit; hpp-cfc
Journal Title: Experimental Hematology
Volume: 20
Issue: 3
ISSN: 0301-472X
Publisher: Elsevier Science, Inc.  
Date Published: 1992-03-01
Start Page: 339
End Page: 349
Language: English
PUBMED: 1373685
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 30 July 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Malcolm A S Moore
    549 Moore