Regulators of endothelial and epithelial barrier integrity and function in acute lung injury.
Regulators of endothelial and epithelial barrier integrity and function in acute lung injury.
复制标题
DOI：
10.1016/j.bcp.2009.01.014
复制
发表时间：
2009-06-15
影响因子：
5.8
通讯作者：
Catravas, John D.
中科院分区：
文献类型：
--
作者：
Lucas, Rudolf;Verin, Alexander D.;Black, Stephen M.;Catravas, John D.
渗透性水肿是伴随急性肺损伤（ALI）、重症肺炎和急性呼吸窘迫综合征（ARDS）的危及生命的并发症，其可与肺泡液体清除（ALC）能力降低、肺泡上皮屏障破坏和毛细血管内皮渗透性增加相关。细菌和病毒感染可直接促进肺内皮细胞通透性增高，并通过在感染的肺中诱导强烈的炎症和氧化应激反应，间接降低II型肺泡上皮细胞中调节ALC的离子转运蛋白的功能和/或表达。除了通气策略外，对于渗透性水肿没有标准的治疗方法，这使得寻找内皮和上皮通透性过高和功能障碍的新调节剂变得重要。在此，我们对最近发现的抑制和/或逆转内皮屏障破坏和通透性或肺泡上皮功能障碍的物质进行了概述：1）锌螯合剂，其被证明可以减轻氧化应激对肺内皮的影响; 2）过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体，通过减少促炎基因的表达; 3）在炎症期间产生的细胞外ATP，其诱导跨肺内皮细胞的跨内皮电阻（TER）的快速和剂量依赖性增加; 4）TNF的凝集素样结构域，其在空间上与受体结合位点不同，并且其保护免于流体静力学和渗透性水肿，和5）Hsp 90抑制剂，其预防和修复毒素诱导的高渗透性。解开这些药物的作用机制可能有助于开发新的治疗策略来对抗渗透性水肿。
Permeability edema is a life-threatening complication accompanying acute lung injury (ALI), severe pneumonia and the acute respiratory distress syndrome (ARDS), which can be associated with a reduced alveolar liquid clearance (ALC) capacity, a disruption of the alveolar epithelial barrier, and an increased capillary endothelial permeability. Bacterial and viral infections can directly promote pulmonary endothelial hyperpermeability and indirectly decrease the function and/or expression of ion transporters regulating ALC in type II alveolar epithelial cells, by means of inducing a strong inflammatory and oxidative stress response in the infected lungs. Apart from ventilation strategies, no standard treatment exists for permeability edema, making the search for novel regulators of endothelial and epithelial hyperpermeability and dysfunction important. Here, we present an overview of recently identified substances that inhibit and/or reverse endothelial barrier disruption and permeability or alveolar epithelial dysfunction: 1) zinc chelators, which were shown to attenuate the effects of oxidative stress on the pulmonary endothelium; 2) peroxisome proliferator activated receptor (PPAR) ligands, which have been shown to exert antiinflammatory effects, by decreasing the expression of pro-inflammatory genes; 3) extracellular ATP, produced during inflammation, which induces a rapid and dose-dependent increase in transendothelial electrical resistance (TER) across pulmonary endothelial cells; 4) the lectin-like domain of TNF, which is spatially distinct from the receptor binding sites and which protects from hydrostatic and permeability edema and 5) Hsp90 inhibitors, which prevent and repair toxin-induced hyperpermeability. Unraveling the mechanism of action of these agents could contribute to the development of novel therapeutic strategies to combat permeability edema.
登录
查看更多内容
DOI：
10.1164/rccm.200702-291oc
发表时间：
2007-10-01
影响因子：
24.7
作者：
Chatterjee, Anuran;Dimitropoulou, Christiana;Catravas, John D.
通讯作者：
Catravas, John D.
影响因子：
21.3
作者：
Connell, P;Ballinger, CA;Patterson, C
通讯作者：
Patterson, C
影响因子：
6.7
作者：
Bodin, P;Burnstock, G
通讯作者：
Burnstock, G
影响因子：
4.8
作者：
Doong, H;Rizzo, K;Kohn, EC
通讯作者：
Kohn, EC
DOI：
10.1165/rcmb.2007-0324oc
发表时间：
2008-11-01
影响因子：
6.4
作者：
Antonov, Alexander;Snead, Connie;Catravas, John D.
通讯作者：
Catravas, John D.