Role of P-selectin in the migration of neutrophils to chemoattractant-induced cutaneous inflammation in mice.
The role of P selectin in the accumulation of neutrophils at acute dermal inflammatory sites induced by chemoattractants, LTB4 and IL-8 was investigated in the mouse. A mouse P-selectin-human IgG chimera bound to mouse neutrophils in vitro in a calcium-dependent manner, as detected by flow cytometry. A rat monoclonal antibody (mAb) against mouse P-selectin, RB40.34 abolished P-selectin-IgG chimera binding to mouse neutrophils, but a control antibody did not. Intradermal injection of LTB4 at a dose of 100 ng/site caused neutrophil accumulation to increase by 3-4 fold, as detected by measuring myeloperoxidase activity. Neutrophil extravasation to perivascular tissue was detected by histochemical observation. The intravenous injection of RB40.34 or the specific LTB4 antagonist, SM-15178, at doses at 5 mg/kg attenuated the accumulation of neutrophils by 55.6% and 70.3%, respectively, but a control antibody showed no effect. Similarly, intradermal administration of IL-8 at a dose of 5 microg/site induced significant neutrophil migration into the interstitial tissue of the skin, as followed by measuring myeloperoxidase activity and histopathologic analysis. The intravenous injection of RB40.34 at a dose of 5 mg/kg reduced the neutrophil accumulation by 59.2% in contrast, a control antibody showed no effect. To our knowledge, this is the first direct demonstration that P-selectin plays a substantial role in LTB4- and IL-8-induced neutrophil accumulation in mouse skin.
Ohnishi
M
M
Sumitomo Pharmaceuticals, Research Center, Osaka, Japan.
Imanishi
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology; D002630:Chemotactic Factors; D003875:Drug Eruptions / Q000473:pathology / Q000503:physiopathology*; D007271:Injections, Intradermal; D016209:Interleukin-8 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors; D016209:Interleukin-8; D019007:P-Selectin; D007975:Leukotriene B4; D009195:Peroxidase