Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide.
The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury, for which the involvement of nitric oxide (NO) and carbon monoxide (CO) has been suggested. NO is induced by NO synthase (NOS) and CO is generated by haeme oxygenase (HO). Among HO isoenzymes, HO-1 is an induced type. To assess the role of NO and CO in the pathogenic process, the cutaneous reverse passive Arthus reaction was examined using NOS inhibitor, HO-1 stimulator and HO-1 inhibitor. To evaluate the reaction we considered oedema, tumour necrosis factor-alpha, interleukin-6, and neutrophil number. The values of these four parameters were significantly reduced in mice treated with HO-1 stimulator as compared with the positive control mice. Quite the reverse was observed in mice treated with HO-1 inhibitor. These results suggest that the HO-1/CO signalling pathway is a therapeutic target for human IC-mediated disease.
Shimizu
K
K
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Bae
S J
SJ
Hara
T
T
Iwata
Y
Y
Yamaoka
T
T
Komura
K
K
Muroi
E
E
Takenaka
M
M
Ogawa
F
F
Sato
S
S
D000818:Animals; D001183:Arthus Reaction / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D002248:Carbon Monoxide / Q000378:metabolism*; D003451:Cryoprotective Agents / Q000378:metabolism*; D005260:Female; D005740:Gases; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000032:analysis; D011524:Protoporphyrins / Q000494:pharmacology; D012867:Skin / Q000276:immunology*; D013053:Spectrophotometry; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D003451:Cryoprotective Agents; D005740:Gases; D015850:Interleukin-6; D009573:Nitrites; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D006427:Hemin; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D051547:Heme Oxygenase-1; D019331:NG-Nitroarginine Methyl Ester