INDUCTION OF NEUTROPHIL INFILTRATION BY RAT CHEMOTACTIC CYTOKINE (CINC) AND ITS INHIBITION BY DEXAMETHASONE IN RATS
INDUCTION OF NEUTROPHIL INFILTRATION BY RAT CHEMOTACTIC CYTOKINE (CINC) AND ITS INHIBITION BY DEXAMETHASONE IN RATS
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DOI：
10.1007/bf00918958
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发表时间：
1992-04-01
期刊：
影响因子：
5.1
通讯作者：
OHUCHI, K
中科院分区：
文献类型：
--
作者：
HIRASAWA, N;WATANABE, M;OHUCHI, K
采用大鼠气囊型炎症模型，观察了大鼠源性白细胞趋化因子（CINC）对中性粒细胞浸润的影响，并观察了地塞米松对CINC诱导的中性粒细胞浸润的影响，以进一步了解糖皮质激素的抗炎作用机制。 将CINC注射到大鼠背部制成的气囊中，在注射后30 min间隔期间，诱导中性粒细胞显著浸润到气囊液中，但未诱导单核细胞和嗜酸性粒细胞浸润。 在1.4 μ g/袋的剂量下诱导最大效应。 在注射CINC前3 h给予地塞米松，可抑制中性粒细胞浸润，呈剂量依赖性，但未观察到完全抑制作用。 当尸体在37 ℃下孵育30分钟时，将CINC注射到已经通过出血而被处死以使来自血流的中性粒细胞浸润最小化的大鼠的气囊中也刺激中性粒细胞浸润到气囊液中，但是浸润的中性粒细胞的数量是完整大鼠中CINC诱导的中性粒细胞浸润的约35%。 CINC诱导的尸体中性粒细胞浸润，这应该是中性粒细胞从皮下组织的血管外空间迁移到囊液的反映，地塞米松治疗没有抑制。 因此，地塞米松抑制中性粒细胞浸润可能是由于抑制外周中性粒细胞外渗，而不是由于抑制中性粒细胞从皮下血管外空间向囊液的趋化性。 这些发现表明，甾体抗炎药对炎症性疾病中中性粒细胞浸润的临床作用部分是由于抑制炎症部位预先形成的中性粒细胞趋化因子诱导的中性粒细胞渗出。
In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammatory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4-mu-g/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutrophil infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37-degrees-C for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact rats. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site.