Endotoxin-induced desensitization for mouse dermal vascular permeability.

内毒素诱导的小鼠真皮血管通透性脱敏。

基本信息

批准号：
09672336
负责人：
FUJII Emiko
金额：
$ 1.86万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Subcutaneous injection of endotoxin (LPS) and some inflammatory mediators to mice increases the dye leakage at the site of injection indicating the increased dermal microvascular permeability. We investigated whether desensitization develops to the increase in permeability elicited by LPS or inflammatory mediators after systemic administration of a single low-dose LPS in male mice. Plasma extravasation was determined by Pontamine sky blue leakage at the site of the skin where LPS and mediators were injected s.c. The dye leakage *duced by LPS, 5-hydroxytryptamine (5-HT), platelet-activating factor, substance P or histamine was significantly decreased by 60-80% in LPS-primed mice, which indicates the development of homologous and heterologous tolerance. Pretreatment with tumor necrosis factor (TNF)-alpha and interleukin (IL)-lalpha but not IL-6 induced the tolerance to LPS, and anti-TNF-alpha antibody and anti-IL-1alpha antibody reversed the LPS-induced tolerance. Homologous tolerance disappeared in the adrenalectomized mice. When mice were pretreated with both LPS and N^G-nitro-L-arginine methyl ester, a nitric oxide (NO) synthase inhibitor, the hyporesponsiveness to LPS and 5-HT disappeared. These results suggest that endogenous cytokines, glucocorticoids and NO may play a role for development of LPS-induced tolerance in microcirculation. The tolerance induced by LPS may provide a potential basis for the treatment of septic shock.

给小鼠皮下注射内毒素（LPS）和一些炎症介质会增加注射部位的染料渗漏，表明真皮微血管通透性增加。我们研究了在雄性小鼠中全身施用单次低剂量 LPS 后，脱敏是否会发展为 LPS 或炎症介质引起的通透性增加。通过皮下注射 LPS 和介质的皮肤部位的 Pontamine 天蓝色渗漏来测定血浆外渗。在LPS引发的小鼠中，由LPS、5-羟色胺(5-HT)、血小板激活因子、P物质或组胺引起的染料渗漏显着减少60-80%，这表明同源和异源耐受性的发展。用肿瘤坏死因子(TNF)-α和白介素(IL)-1α而不是IL-6预处理诱导对LPS的耐受，并且抗TNF-α抗体和抗IL-1α抗体逆转了LPS诱导的耐受。同源耐受性在肾上腺切除小鼠中消失。当小鼠同时接受 LPS 和 N^G-硝基-L-精氨酸甲酯（一种一氧化氮 (NO) 合酶抑制剂）预处理时，对 LPS 和 5-HT 的低反应性消失了。这些结果表明，内源性细胞因子、糖皮质激素和 NO 可能在 LPS 诱导的微循环耐受性的发展中发挥作用。 LPS诱导的耐受可能为感染性休克的治疗提供潜在的基础。