Role of P-selectin in the early stage of the Arthus reaction.
P-selectin is rapidly translocated to the surface of endothelial cells and platelets following exposure to chemical mediators such as histamine, thrombin and complement factors. The Arthus reaction is caused by vascular injury which is initiated by the local deposition of the immune complex followed by the activation of complement and release of chemical mediators. In this report, the role of P-selectin in the early stage of reverse passive Arthus reaction in rat using monoclonal antibodies (mAbs) against rat P-selectin will be investigated. Intravenous administration of the mAb ARP2-4 significantly attenuated paw edema 1 h after challenging it with antigen by 31.5% (1 mg/kg) and 44.7% (3 mg/kg), respectively. Edema formation was also reduced by sulfatide (73.1%, 50 mg/kg) and inositol hexakisphosphate (InsP6) (72.9%, 30 mg/kg), which have been reported to block P-selectin-mediated neutrophil adhesion. Moreover, neutrophil accumulation into the inflammatory site in the Arthus reaction was inhibited by anti-P-selectin mAb. P-selectin expression was detected along vessel walls prior to neutrophil accumulation, as determined by immunohistochemical staining using the antibody. In addition, the expression of P-selectin mRNA was induced 4 h after deposition of immune complex. From these results, we concluded that P-selectin plays an important role in the pathogenesis of the Arthus reaction especially in the early stage by recruiting neutrophils into sites of inflammation.
Ohnishi
M
M
Research Center, Sumitomo Pharmaceuticals Co. Ltd., Osaka, Japan.
Koike
H
H
Kawamura
N
N
Tojo
S J
SJ
Hayashi
M
M
Morooka
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001183:Arthus Reaction / Q000209:etiology*; D001550:Benzamidines; D015152:Blotting, Northern; D004487:Edema / Q000209:etiology; D006146:Guanidines / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D019007:P-Selectin / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D001550:Benzamidines; D006146:Guanidines; D006633:Histamine Antagonists; D019007:P-Selectin; D012333:RNA, Messenger; C032855:nafamostat