Hematopoietic growth factors upregulate the p65 type II interleukin-1 receptor on bone marrow progenitor cells in vitro.
Having previously shown that interleukin-1 (IL-1) induces the expression of IL-1 receptors (IL-1Rs) on bone marrow (BM) cells in vivo through an indirect mechanism, we studied whether hematopoietic growth factors (HGFs) could induce the expression of IL-1R on BM cells in vitro. In vitro treatment of light-density murine BM (LDBM) cells with either IL-3, IL-6, granulocyte--colony-stimulating factor (CSF), or granulocyte-macrophage--CSF caused a 5- to 10-fold upregulation of IL-1R expression, whereas IL-1, IL-5, IL-7, and macrophage-CSF had no effect. Scatchard analysis showed one class of IL-1Rs on LDBM cells with an average of 66 +/- 20 sites per cells. After 24 hours of treatment with IL-3, the number of IL-1Rs increased to 413 +/- 125, without effecting the affinity. This effect required protein synthesis, but was independent of cell division. Purified lineage-negative progenitor cells (Lin-) did not express detectable levels of IL-1R, but 24 hours of treatment with IL-3, GM-CSF, and G-CSF stimulated IL-1--specific binding. Autoradiographic analysis of Lin- cells showed that IL-1R induction by IL-3 occurs on undifferentiated blast cells. Affinity labeling of Lin- cells treated with HGFs showed an increase in a 65-Kd IL-1 binding protein that did not bind or compete with an anti-type I IL-1R antibody, suggesting that these cells expressed type II IL-1R. These data suggest that IL-1 stimulation of myelopoiesis occurs by a mechanism involving IL-1R upregulation on hematopoietic progenitor cells by HGFs.
Dubois
C M
CM
Laboratory of Immunoregulation, National Cancer Institute (NCI), Frederick, MD.
Ruscetti
F W
FW
Jacobsen
S E
SE
Oppenheim
J J
JJ
Keller
J R
JR
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1; D007377:Interleukin-3; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor