Modulation of endotoxin-induced histamine synthesis by cytokines in mouse bone marrow-derived macrophages

J Immunol. 1996 Jan 15;156(2):778-85.


The aim of this study was to examine the roles of various cytokines in histamine synthesis by macrophages in bone marrow. Pure (> 99% nonspecific esterase-, CD14-, and Mac-1-positive) macrophage populations were obtained after long term culture of bone marrow cells (bone marrow-derived macrophages). Culture of the cells in the presence of Escherichia coli LPS caused a slight, but dose-dependent, increase in histidine decarboxylase-associated histamine synthesis with a concomitant increase in the expression of CD14, a LPS receptor, as well as the Mac-1 Ag on their surface. Granulocyte/macrophage CSF (GM-CSF) or IL-3 strongly enhanced LPS-induced histamine formation and expression of CD14 on bone marrow-derived macrophages, without affecting the expression of Mac-1 Ag. GM-CSF and IL-3 also caused a marked accumulation of both histidine decarboxylase and IL-6 mRNAs in the cells. Macrophage CSF and IL-1-alpha also potentiated LPS-dependent histamine formation when it was stimulated with GM-CSF or IL-3. In contrast to these cytokines, IFN-gamma suppressed LPS-induced histamine production regardless of whether it was stimulated by GM-CSF or IL-3, and inhibited CD14 expression. Neither IL-6 nor granulocyte CSF had any appreciable effect on LPS-induced histamine production even in combination with GM-CSF or IL-3. These results suggest that GM-CSF and IL-3 enhance LPS-induced histamine production in bone marrow-derived macrophages and that macrophage CSF and IL-1 alpha augment the actions of GM-CSF and IL-3. Possible implication of CD14 molecule in the reactions is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Bone Marrow Cells*
  • Cells, Cultured
  • Cytokines / pharmacology*
  • Endotoxins / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Histamine / biosynthesis*
  • Histidine Decarboxylase / metabolism
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-6 / pharmacology
  • Lipopolysaccharide Receptors / analysis
  • Lipopolysaccharide Receptors / physiology
  • Lipopolysaccharides / pharmacology*
  • Macrophage-1 Antigen / analysis
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Mutant Strains
  • Recombinant Proteins / pharmacology


  • Biomarkers
  • Cytokines
  • Endotoxins
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Macrophage-1 Antigen
  • Recombinant Proteins
  • endotoxin, Escherichia coli
  • Histamine
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Histidine Decarboxylase