Histamine enhances granulocyte-macrophage colony-stimulating factor and interleukin-6 production by human peripheral blood mononuclear cells.
The effect of histamine on the production of cytokines by subpopulations of mononuclear cells was studied. A 3.5-fold increase in the number of myeloid colony-forming units (CFU-C) was observed when bone marrow cells were cultured in the presence of conditioned medium prepared from nonadherent mononuclear cells cultured with 10(-4) M histamine (CM-histamine) compared with phosphate-buffered saline (CM-PBS). Using ELISA and radioimmunoassay kits, histamine was found to enhance the production of GM-CSF (9.6-fold) and IL-6 (8.2-fold) by mononuclear cells but not by nonadherent cells or large granular lymphocytes. Anti-GM-CSF and anti-IL-6 antibodies markedly blocked cytokine activity in CM-PBS, whereas the blocking effect in CM-histamine was moderate, indicating enhanced GM-CSF and IL-6 activity in CM-histamine. No GM-CSF or IL-6 levels could be detected in CM-histamine or CM-PBS prepared from CD3+, CD4+, or CD8+ lymphocytes. Preincubation of CM-histamine with H1 and H2 receptor antagonists resulted in complete blocking of the histamine-enhanced colony-stimulating activity. We conclude that histamine is able to activate human mononuclear cells to generate cytokines such as GM-CSF and IL-6 via H1 and H2 receptors.
Mor
S
S
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Nagler
A
A
Barak
V
V
Handzel
Z T
ZT
Geller-Bernstein
C
C
Fabian
I
I
D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000276:immunology; D006632:Histamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011738:Pyrilamine / Q000494:pharmacology; D011863:Radioimmunoassay; D011899:Ranitidine / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013268:Stimulation, Chemical; D016593:Terfenadine / Q000494:pharmacology
D000906:Antibodies; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007377:Interleukin-3; D015850:Interleukin-6; D016593:Terfenadine; D002927:Cimetidine; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011899:Ranitidine; D011738:Pyrilamine