THE ROLE OF LIPID A IN ENDOTOXIN-INDUCED UVEITIS

脂质 A 在内毒素引起的葡萄膜炎中的作用

• 批准号: 06671751
• 负责人: FUJINO Yujiro
• 金额: $ 1.34万
• 依托单位: UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671751/
• 关键词: Endotoxin-induced Uveitis; Lipopolysaccharide; Lipid A; Cytokine-induced Neutrophil Chemoattractant; Neutrophil; リピッドA; ぶどう膜炎; エンドトキシン; Lipid A

Part I-Comparative clinical study of LPS and LA groupsThe LPS and LA successfully induced uveitis and the peak of the ocular inflammation was obtained with 1000 mug/kg and 100 mug/kg, respectively. Cells in the AC were more numerous in the LA group than the LPS group at any given level of protein concentration.Part II-Analysis of the CINC family in LPS and LA groupsThe time course variation in the CINC family concentration in AH and serum samples obtained from both LPS and LA groups was assessed by EIA.The CINC-1 level in AH showed higher concentration in the LPS group compared to the LA group. The serum level of CINC-1 peaked at 6 hours in both groups and was also significantly higher in the LPS-group. The AH fromthe LPS group possessed stronger chemoattractant activity than the AH from the LA group. The evaluation of the cell infiltration into the AC in the rats injected with intravenous recombinant CINC-1 revealed that CINC-1 inhibited the migration of the inflammatory cells into the AC in a dose-dependent manner.It has already been reported that CINC-1, when present at concentrations over 10 ng/mL,promotes the shedding of L-selectin from the neutrophil membrane, which disables the neutrophils to interact with vascular endothelium. Thus, the high level of CINC-1 in the intravascular compartment of the LPS model seemed to be a plausible altemative to explain the lower cell migration into the AC.The LA-induced uveitis induced more inflammation in the eye than did the LPS-induced uveitis, without altering excessively the systemic homeostasis. These findings should be considered for further selection of uveitis model.

第一部分LPS组与LA组的比较临床研究LPS组和LA组均成功诱导葡萄膜炎，分别在1000杯/kg和100杯/kg剂量下达到眼部炎症的峰值。在任何给定的蛋白质浓度水平下，LA组AC中的细胞数量都比LPS组多。第二部分- LPS组和LA组中CINC家族的分析通过EIA评估LPS组和LA组AH和血清样本中CINC家族浓度的时间变化。与LA组相比，LPS组AH中CINC-1水平升高。两组血清cinc1水平均在6小时达到峰值，lps组血清cinc1水平也显著高于lps组。LPS组的AH具有比LA组更强的趋化活性。对静脉注射重组cinc1大鼠细胞向AC的浸润情况的评价显示，cinc1抑制炎症细胞向AC的迁移呈剂量依赖性。已有报道称，当浓度超过10 ng/mL时，CINC-1可促进中性粒细胞膜上l -选择素的脱落，从而使中性粒细胞无法与血管内皮相互作用。因此，LPS模型的血管内腔室中高水平的CINC-1似乎是解释细胞向ac迁移较低的一个合理的选择。la诱导的葡萄膜炎比LPS诱导的葡萄膜炎在眼睛中诱导更多的炎症，而不会过度改变系统稳态。这些结果应作为进一步选择葡萄膜炎模型的参考。