Granulocyte macrophage-colony stimulating factor increases the expression of histamine and histamine receptors in monocytes/macrophages in relation to arteriosclerosis.
OBJECTIVE
To study the effect of granulocyte macrophage-colony-stimulating factor (GM-CSF) on histamine metabolism in arteriosclerosis, the expression of histidine decarboxylase (HDC; histamine-producing enzyme), histamine receptors 1 and 2 (HH1R and HH2R), and GM-CSF was investigated in human and mouse arteriosclerotic carotid arteries. Furthermore, the molecular mechanisms of GM-CSF-induced HDC and HH1R expression in monocytic U937 cells were investigated.


RESULTS
Immunohistochemistry showed that atherosclerotic human coronary and mouse ligated carotid arteries contained HDC-expressing macrophages. Gene expression of HDC, HH1R, HH2R, and GM-CSF was also detected in the lesions. In U937 cells, GM-CSF enhanced histamine secretion and gene expression of HDC and HH1R. A promoter assay showed that GM-CSF enhanced gene transcription of HDC and HH1R but not HH2R.


CONCLUSIONS
The present results indicate that HDC and HHR are expressed in arteriosclerotic lesion, and that GM-CSF induces HDC and HH1R expression in monocytes. Locally produced histamine might participate in atherogenesis by affecting the expression of atherosclerosis-related genes in monocytes and smooth muscle cells. The presence of histamine-producing macrophages and gene expression of histamine receptors and GM-CSF was demonstrated in arteriosclerotic lesions. In monocytic U937 cells, GM-CSF upregulated the expression of histamine and HH1R. Coordinated expression of histamine and its receptors by GM-CSF would participate in atherogenesis by affecting monocytic and SMC gene expression.
Murata
Yoshitaka
Y
Kyurin Omtest Laboratory, Kyurin Corporation, Yahatanishi-ku, Kitakyushu, Japan.
Tanimoto
Akihide
A
Wang
Ke-Yong
KY
Tsutsui
Masato
M
Sasaguri
Yasuyuki
Y
De Corte
Filip
F
Matsushita
Hiroshi
H
D000818:Animals; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D006632:Histamine / Q000096:biosynthesis*; D006636:Histamine Release / Q000187:drug effects; D006640:Histidine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D008026:Ligation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000096:biosynthesis* / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects; D017539:Tunica Intima / Q000473:pathology; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018808:Transcription Factor AP-1; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006640:Histidine Decarboxylase