THE EFFECTS OF ENDOTHELIN ON ENOTIN-INDUCED PULMONARY VASCULAR IACM-1 EXPRESSION AND ITS APPLICATION TO THE THERAPEUTIC STRATEGY OF ACUTE LUNG INJURY

内皮素-1（ET-1）和一氧化氮（NO）在肺血管张力的控制中起相反的作用。最近，这些血管活性物质被认为是局部血管内皮细胞的稳态调节剂。在炎症部位，血管内皮细胞被激活，内皮细胞表面的内皮细胞-白细胞粘附分子如细胞间粘附分子-1（ICAM-1）表达上调，本研究观察了ET-1和NO对培养的人肺微血管内皮细胞（HPMVEC）ICAM-1表达的影响。主要研究结果如下：1.在非刺激状态下，ET-1和NO对HPMVEC表达ICAM-1无影响.细胞表面酶免疫分析表明，NO以剂量依赖性方式抑制内毒素（LPS）刺激的ICAM-1表达30-50%。ET-1对LPS刺激的ICAM-1表达无影响.免疫荧光研究表明，NO抑制ICAM-1表达的机制部分涉及抑制跨核定位转录核因子-CB（NF-κB B）。我们目前的研究提供了NO和白细胞之间的联系，并提供线索，这种效果的机制。我们推测，针对NF-κB的调节策略的发展可能为治疗肺部炎症性疾病提供新的治疗工具。

Endothelin-1 (ET-1) and Nitric Oxide (NO) play an opposing role in the control of pulmonary vascular tone. Recently, these vasoactive substances have recognized as homeostatic regulator of local vascular endothelial cells. At the site of inflammation, vascular endothelial cells are activated and endothelial-leukocyte adhesion molecules such as intercellular adhesion molecule-l (ICAM-1) are up regulated on the surface of endothelial cells.In this project, we examined the impact of ET-1 and NO on ICAM-1 expression on cultured human pulmonary microvascular endothelial cells (HPMVEC). The results are summarized as below:1. Under unstimulated state, neither ET-1 nor NO had any effects on ICAM-1 expression on HPMVEC.2. NO inhibited endotoxin (LPS)-stimulated ICAM-1 expression in a dose dependent manner by 30-50% as determined by cell surface enzyme immunoassays. In contrast, ET-1 had no effect on LPS-stimulated ICAM-1 expression.3. Immunofluorescence study indicates that the mechanism by which NO inhibits ICAM-1 expression, in part, involves inhibition of transnuclear location transcriptional nuclear factor-CB (NF-κB).Several lines of evidence have recently suggested a role for NO as an antileukocyte autacoid. Our present study provides a link between NO and leukocyte and offers clues as to the mechanism of such an effect. We speculate development of modulatory strategies targeting NF-κB my provide a novel therapeutic tool for the treatment of lung inflammatory disease.