Characterization and pharmacological modulation of antigen‐induced peritonitis in actively sensitized mice
Characterization and pharmacological modulation of antigen‐induced peritonitis in actively sensitized mice
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主动致敏小鼠抗原诱导腹膜炎的特征和药理学调节
DOI：
10.1111/j.1476-5381.1993.tb13900.x
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发表时间：
1993
影响因子：
7.3
通讯作者：
M. Pretolani
中科院分区：
文献类型：
--
作者：
C. Zuany‐Amorim;D. Leduc;B. Vargaftig;M. Pretolani
1腹膜内（i. p.）给致敏Balb/c小鼠注射1或10 μg卵清蛋白可引起急性组胺释放，首先在激发后1分钟出现，30分钟后恢复到基础水平。这种现象不伴有蛋白质外渗。在1或10 μg卵清蛋白给药后6 h，在致敏小鼠的腹腔冲洗液中观察到免疫反应性白三烯（LT）C4和LTB 4的量呈剂量依赖性增加。在单独的实验中，向未免疫小鼠腹膜内给予1 mg活化酵母聚糖后，小鼠腹膜中出现明显的蛋白质外渗，并在注射后1 h释放免疫反应性LTC 4和LTB 4，但不释放组胺。2小鼠腹腔介质的释放伴随着短暂的中性粒细胞浸润，在6 h达到高峰，此后恢复到基础水平。还观察到从24 h开始的强烈嗜酸性粒细胞蓄积，在48 h达到峰值，并在164 h恢复至基础值。3用地塞米松（1 mg kg−1，s.c.）预处理动物可减少24 h时观察到的卵清蛋白（1 μg）诱导的嗜酸性粒细胞增多症。或5-脂氧合酶抑制剂BWA 4C（20 mg kg−1，s.c.），而吲哚美辛（2 mg kg-1，s.c.）和血小板活化因子（PAF）拮抗剂SR 27417（10 mg kg−1，s.c.）是无效的。这些结果表明，脂氧合酶途径的花生四烯酸代谢物（而非环加氧酶衍生物或PAF）介导抗原诱导的小鼠腹膜中嗜酸性粒细胞蓄积。4组胺H1受体拮抗剂药物西替利嗪（15-30 mg kg−1，s.c.）在特非那定无效的条件下，显着降低卵清蛋白诱导的嗜酸性粒细胞蓄积，表明西替利嗪的作用与组胺H1受体作用的抑制无关。5免疫抑制剂FK-506（1-2 mg kg-1，s.c.）和蛋白质合成抑制剂环己酰亚胺，当原位（0.06 ng/腔）或全身（5 mg kg-1，s.c.）给药时，防止抗原诱导的小鼠腹膜中嗜酸性粒细胞蓄积，这有助于说明来源于淋巴细胞的物质（可能是细胞因子）可能参与该模型中嗜酸性粒细胞趋化反应的调节。6本研究的结果表明，对主动致敏小鼠腹腔注射卵清蛋白可诱导晚期嗜酸性粒细胞在腹腔内积聚。这种现象可能部分由脂氧合酶代谢产物的释放和/或新产生的因子（如T淋巴细胞衍生的嗜酸性粒细胞趋化性细胞因子）介导，为研究抗过敏和抗炎药物的作用机制提供了一种有趣的工具。
1 The intraperitoneal (i.p.) injection of 1 or 10 μg ovalbumin to sensitized Balb/c mice led to an acute histamine release, firstly evidenced 1 min after the challenge and returning to basal levels 30 min thereafter. This phenomenon was unaccompanied by protein extravasation. A dose‐dependent increase in the amounts of immunoreactive leukotriene (LT) C4 and LTB4 was observed in the peritoneal washing from sensitized mice 6 h after 1 or 10 μg ovalbumin administration. In separate experiments, the i.p. administration of 1 mg activated zymosan to non‐immunized mice was followed by a marked protein extravasation, and by immunoreactive LTC4 and LTB4, but not histamine, release in mouse peritoneum 1 h after its injection. 2 Mediator release in the mice peritoneal cavity was concomitant with a transient neutrophil infiltration, which peaked at 6 h and returned to basal levels thereafter. An intense eosinophil accumulation starting at 24 h, peaking at 48 h and returning to basal values at 164 h, was also observed. 3 Ovalbumin (1 μg)‐induced eosinophilia, observed at 24 h, was reduced by the pretreatment of the animals with dexamethasone (1 mg kg−1, s.c.) or with the 5‐lipoxygenase inhibitor, BWA4C (20 mg kg−1, s.c.), whereas indomethacin (2 mg kg−1, s.c.) and the platelet‐activating factor (PAF)‐antagonist SR 27417 (10 mg kg−1, s.c.) were ineffective. These results indicate that metabolites of arachidonic acid of lipoxygenase pathway, but not cyclo‐oxygenase derivatives or PAF, mediate antigen‐induced eosinophil accumulation in the mouse peritoneum. 4 The histamine H1 receptor antagonist drug, cetirizine (15–30 mg kg−1, s.c.) markedly reduced ovalbumin‐induced eosinophil accumulation under conditions where terfenadine was ineffective, suggesting that the effect of cetirizine was not related to the inhibition of the H1 receptor effects of histamine. 5 The immunosuppressive agent, FK‐506 (1–2 mg kg−1, s.c.) and the protein synthesis inhibitor, cylcoheximide, when administered either in situ (0.06 ng/cavity) or systemically (5 mg kg−1, s.c.), prevented antigen‐induced eosinophil accumulation in the mouse peritoneum, contributing to the concept that substances (probably cytokines) originating from lymphocytes may be involved in the modulation of the eosinophilotactic response in this model. 6 The results of the present study indicate that the i.p. administration of ovalbumin to actively sensitized mice induced late eosinophil accumulation in the peritoneal cavity. This phenomenon, which may be in part mediated by the release of lipoxygenase metabolites and/or by newly generated factors, such as T‐lymphocytes‐derived eosinophilotactic cytokines, offers an interesting tool to investigate the mechanism of action of anti‐allergic and anti‐inflammatory drugs.
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糖皮质激素对炎症细胞的影响与其在哮喘中的治疗应用相关。
DOI：
--
发表时间：
1990
期刊：
The American review of respiratory disease
影响因子：
--
作者：
Schleimer,RP
通讯作者：
Schleimer,RP
影响因子：
15.9
作者：
LOPEZ, AF;WILLIAMSON, DJ;VADAS, MA
通讯作者：
VADAS, MA
影响因子：
14.2
作者：
GLEICH, GJ
通讯作者：
GLEICH, GJ
DOI：
--
发表时间：
1990
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Secor,WE;Stewart,SJ;Colley,DG
通讯作者：
Colley,DG
人类嗜酸性粒细胞的存活时间更长，功能特性增强，并且在暴露于人类白细胞介素 3 时会变得低密度。
DOI：
10.1172/jci113547
发表时间：
1988
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Rothenberg,ME;OwenJr,WF;Silberstein,DS;Woods,J;Soberman,RJ;Austen,KF;Stevens,RL
通讯作者：
Stevens,RL