Hematopoietic growth factors upregulate the p65 type II interleukin-1 receptor on bone marrow progenitor cells in vitro

Blood. 1992 Aug 1;80(3):600-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow / immunology
  • Cell Line
  • Cells, Cultured
  • Cytokines / pharmacology*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Hematopoietic Cell Growth Factors / pharmacology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / immunology*
  • Interleukin-1 / metabolism*
  • Interleukin-1 / pharmacology
  • Interleukin-3 / pharmacology
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / metabolism*
  • Receptors, Interleukin-1
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Up-Regulation

Substances

  • Cytokines
  • Hematopoietic Cell Growth Factors
  • Interleukin-1
  • Interleukin-3
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor