[The inhibitory effect of LTB4 antagonist on eosinophil infiltration in cutaneous and gut late phase response in BALB/C mice sensitized with ovalubumin (OVA)].

Article

作者: Hakugawa, J ; Tanaka, Y ; Vinuesa, M A ; Bae, S J ; Katayama, I

In this study we investigated the effect of LTB4 antagonist on eosinophil infiltration in skin and gut late phase response (LPR) in OVA-sensitized BALB/c mice. The eosinophil infiltrations to skin and gut induced by skin and oral challenge reached a peak at 12 h and 6 h after the challenge, respectively. Intraperitoneal administration of LTB4 antagonist (ONO-4057) before the challenge significantly inhibited eosinophil infiltrations to the skin and gut by 53.3% and 73.7%, respectively (p < 0.05). Next, we investigated the effect to that by PAF antagonist (ONO-6240) and anti-IL-5 mAb in the skin system. OVA-induced eosinophil infiltration at 12 h after intracutaneous challenge was significantly inhibited by peritoneal administration of anti-IL-5 mAb before the challenge by 89.6% (p < 0.05), but not by that of PAF antagonist. Our results demonstrated the inhibitory effect of LTB4 antagonist on eosinophil infiltration in skin and gut LPR, suggesting the potency of LTB4 antagonist for treatment of skin lesion and food allergy in atopic dermatitis considered to be associated with LPR.

1995-11-01·Zhonghua nei ke za zhi

[Effects of a platelet-activating factor antagonist ONO-6240 on antigen induced eosinophil infiltration into the airways].

Article

作者: Shi, H ; Xu, H ; Liang, G

An in vivo mouse model of allergic bronchial asthma was developed to investigate the effects of a platelet activating factor antagonist ONO-6240 on eosinophil (EOS) recruitment into the mouse airway. In the present study, no EOS could be found in bronchoalveolar lavage fluid (BALF) from normal control mice. However, chronic ovalbumin challenge of sensitized mice induced significant bronchoalveolar eosinophilia (9.68 +/- 0.72 x 10(8)/L). In three groups of mice treated intraperitoneally with different doses of ONO-6240 (0.1, 1.0, 10.0 mg/kg), the medication produced 42.1% (5.60 +/- 0.97 x 10(8)/L, P < 0.01), 58.8% (3.99 +/- 0.84 x 10(8)/L, P < 0.01), and 72.6% (2.65 +/- 0.71 x 10(8)/L, P < 0.01) inhibition, respectively, of the antigen-induced influx of EOS into BALF. It was found that the prevention of EOS infiltration into airway with ONO-6240 was accompanied by decrements of both interleukin (IL)-5 and IL-2 levels. These data indicated that ONO-6240 prevented airway eosinophilia by inhibiting production of IL-5 and IL-2. Our results suggested that ONO-6240 may be of value in treating human asthmatic patients.

1992-01-01·The Japanese Journal of Pharmacology

Antagonism of Platelet-Activating Factor-Induced Increase in Cytosolic Free Calcium Concentration in Human Endothelial Cells.

Article

作者: Masahiko Hirafuji ; Hisashi Shinoda

The effects of platelet-activating factor (PAF) antagonists on the agonist-induced increase in cytosolic free calcium concentration, [Ca2+]i, in human vascular endothelial cells grown in monolayer were investigated by a continuous superfusion technique using a calcium fluorescent probe, fura-2. PAF caused a small but dose-dependent increase in [Ca2+]i. Seven structurally dissimilar PAF antagonists dose-dependently suppressed the peak response, among which WEB 2086 was the most potent, followed by WEB 2170 greater than FR 900452 not equal to ONO 6240 greater than BN 52021 not equal to kadsurenone not equal to CV 3988. These antagonists except for CV 3988 were specific for PAF, since they had no effects on calcium mobilization induced by thrombin or histamine, while CV 3988 had a non-specific effect. PAF in the same range of concentration increased prostacyclin release from human endothelial cells. WEB 2086 also inhibited the PAF-induced prostacyclin release, while it had not effect on the release induced by histamine and thrombin. These results demonstrate the specificity and dose-response characteristics of PAF antagonists in cultured human endothelial cells and suggest that a PAF antagonist could be a valuable therapeutic agent in certain human diseases where PAF activation of endothelial cells may have a critical role.

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适应症	最高研发状态	国家/地区	公司	日期
休克	临床2期	日本	Ono Pharmaceutical Co., Ltd.	1986-02-01
肠坏死	临床前	美国	Sandoz Research Institute	1986-04-01
肠坏死	临床前	美国	Northwestern University	1986-04-01
休克	临床前	日本	Shinshu University School of Medicine	1986-02-01