Modulation of endotoxin-induced histamine synthesis by cytokines in mouse bone marrow-derived macrophages.
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.
Nagoya University Bioscience Center, Japan.
S
S
Takamatsu
I
I
Nakashima
K
K
Nakano
D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006632:Histamine / Q000096:biosynthesis*; D006640:Histidine Decarboxylase / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000032:analysis; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D015415:Biomarkers; D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; C044101:endotoxin, Escherichia coli; D006632:Histamine; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006640:Histidine Decarboxylase