Characterization of murine hematopoietic progenitor subsets involved in interleukin-3-induced interleukin-6 production.
Various murine cell populations were tested for their ability to generate interleukin-6 (IL-6) in response to IL-3. Among these, bone marrow cells exhibit the most prominent IL-6 production. The responder cells in this organ have been further characterized by cell fractionation on a discontinuous Ficoll gradient, fluorescence-activated cell sorting, and in situ hybridization. These procedures have allowed us to ascribe the following features to the cells mainly responsible for IL-3-induced IL-6 production: (1) they possess a low density and a relatively high forward and perpendicular light scatter (FLS/PLS); (2) they are characterized by a high rhodamine (Rh) retention; and (3) their enrichment in various subpopulations is similar to that obtained for progenitors forming colonies in the methylcellulose assay colony-forming units (CFU-C). In contrast, IL-3 target cells in terms of IL-6 production are absent both in the mature and in the most immature bone marrow compartment. Indeed, the Rh-dull population that is enriched for cells with marrow repopulating activity does not respond to the growth factor and mature cells cannot be induced to express IL-6 as assessed by (1) FLS/PLS characteristics, (2) the monoclonal antibody ER-MP 20 recognizing monocytes and granulocytic cells, and (3) in situ hybridization. Taken together, our data support the conclusion that the bone marrow cells generating IL-6 in response to IL-3 belong to a progenitor population with enhanced mitochondrial activity, comprising probably several types of immature cells of the myeloid lineage including macrophage/granulocyte precursors.
Schneider
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E
CNRS URA 1461, Hôpital Necker, Paris, France.
Ploemacher
R E
RE
Navarro
S
S
van Beurden
C
C
Dy
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002469:Cell Separation; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D003114:Colony-Forming Units Assay; D003470:Culture Media; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003470:Culture Media; D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins