Watanabe M, Sugidachi A, Omata M, Hirasawa N, Mue S, Tsurufuji S, Ohuchi K
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Int Arch Allergy Appl Immunol. 1990;92(4):396-403. doi: 10.1159/000235171.
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.
通过将抗原溶液注射到用偶氮苯 - 砷酸盐 - 共轭乙酰牛血清白蛋白免疫的大鼠背部制成的气袋中诱导过敏炎症。在该模型中，抗原攻击后4 - 8小时，白细胞向气袋液中的浸润显著。大多数浸润的白细胞是中性粒细胞。在抗原攻击前15分钟和攻击时，将血小板活化因子（PAF）拮抗剂如CV - 3988和L - 652,731注入气袋，未能在8小时时抑制白细胞浸润。然而，当在抗原攻击后4小时将PAF拮抗剂注入气袋时，8小时时的中性粒细胞浸润以剂量依赖的方式受到抑制。5 - 脂氧合酶抑制剂AA861与PAF拮抗剂联合治疗并未增强PAF拮抗剂的作用，表明白三烯B4在该模型中性粒细胞浸润中的参与可忽略不计。8小时时嗜酸性粒细胞浸润非常弱，PAF拮抗剂未显示出显著作用。8小时时，免疫大鼠血清中的PAF水平显著高于未免疫大鼠。在抗原攻击前15分钟静脉注射PAF拮抗剂比局部注入气袋更有效地抑制白细胞浸润。这些结果表明PAF在过敏性炎症的中性粒细胞浸润中起重要作用。
