Possible role for platelet-activating factor in neutrophil infiltration in allergic inflammation in rats.
Allergic inflammation was induced by injecting an antigen solution into an air pouch made on the dorsum of immunized rats with the antigen azobenzene-arsonate-conjugated acetyl bovine serum albumin. In this model, leukocyte infiltration into the pouch fluid was prominent 4-8 h after the antigen challenge. Most of the infiltrated leukocytes were neutrophils. Administration of the platelet-activating factor (PAF) antagonists such as CV-3988 and L-652,731 into the air pouch 15 min before and at the time of the antigen challenge failed to suppress leukocyte infiltration at 8 h. However, when the PAF antagonist was injected into an air pouch 4 h after the antigen challenge, neutrophil infiltration at 8 h was suppressed in a dose-dependent manner. Combined treatment with the 5-lipoxygenase inhibitor AA861 and the PAF antagonist did not potentiate the effect of the PAF antagonist, suggesting that participation of leukotriene B4 in neutrophil infiltration in this model is negligible. Eosinophil infiltration was very weak at 8 h, and the PAF antagonist showed no significant effect. At 8 h, the PAF level in the serum of the immunized rats was significantly higher than that of the nonimmunized rats. Intravenous administration of the PAF antagonist 15 min before the antigen challenge suppressed leukocyte infiltration more effectively than local administration into the pouch. These results indicate that PAF plays a significant role in neutrophil infiltration in allergic inflammation.
Watanabe
M
M
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Sugidachi
A
A
Omata
M
M
Hirasawa
N
N
Mue
S
S
Tsurufuji
S
S
Ohuchi
K
K
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D006967:Hypersensitivity / Q000473:pathology*; D007114:Immunization; D007249:Inflammation / Q000473:pathology*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology*; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D016227:Benzoquinones; D005663:Furans; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C037913:CV 3988; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran