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.

皮下注射内毒素（LPS）和一些对小鼠的炎症介质会增加注射部位的染料泄漏，表明皮肤微血管通透性增加。我们研究了脱敏是否发展为在全身给雄性小鼠单一低剂量LPS全身给药后引起的LPS或炎症介质引起的渗透性增加。血浆渗出是通过向S.C.注入LPS和介体的皮肤部位的Pontamine Sky Blue泄漏确定的。 LPS培养的小鼠在LPS，5-Hydroxyptamine（5-HT），血小板激活因子，物质P或组胺引起的染料泄漏 *在LPS培养的小鼠中显着降低了60-80％，这表明同源和异型耐受性的发展。用肿瘤坏死因子（TNF）-Alpha和白介素（IL）-Lalpha进行预处理，而IL-6不诱导对LPS的耐受性，抗TNF-Alpha抗体和抗IL-1Alpha抗体逆转LPS诱导的耐受性。同源耐受性消失在肾上腺切除小鼠中。当小鼠用LPS和N^G-硝基-l-精氨酸甲酯（NO）合成酶抑制剂预处理时，对LPS的低温和5-HT消失了。这些结果表明，内源性细胞因子，糖皮质激素和NO可能在微循环中LPS诱导的耐受性的发展起作用。 LPS引起的公差可能为治疗败血性休克的治疗提供潜在的基础。