Aminothiol WR-1065 protects endothelial cell morphology against alterations induced by lipopolysaccharide.
Aminothiol WR-1065 protects endothelial cell morphology against alterations induced by lipopolysaccharide.
复制标题
氨基硫醇 WR-1065 可保护内皮细胞形态免受脂多糖诱导的改变。
DOI：
10.1097/00024382-199812000-00009
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Rubin,DB
中科院分区：
文献类型：
--
作者：
Podolski,JL;Mooteri,SN;Drab-Weiss,EA;Onoda,JM;Saclarides,TJ;Rubin,DB
在脓毒症患者中，脂多糖（LPS）损伤血管内皮，其表现为组织水肿和愈合受损。当LPS通过产生自由基部分地扭曲内皮细胞形态时，这种病理发生。在先前的研究中发现了一种清除自由基的放射性保护剂，氨基硫醇WR-1065（[N-2-巯基乙基]-1-3-二氨基丙烷），其使辐照的内皮细胞的形态正常化（Mooteri SN，Podolski JL，Drab EA，等人：Radiat Res 145：217-224，1996）。本研究的目的是确定WR-1065是否也使暴露于LPS后的内皮细胞形态正常化。为此，将牛主动脉内皮细胞培养物的部分裸露并暴露于1 ng/mL的LPS。30分钟后，顶端膜表达增加的纤连蛋白整合素受体，[α] 5 [β] 1。5 h后，前缘细胞形态发生畸变，细胞间接触减少。此外，丝状肌动蛋白应力纤维消散，然而，丝状肌动蛋白含量每细胞不变。在LPS暴露之前用2 mM WR-1065处理2小时减弱了[α] 5 [β] 1表达的增加，并促进了迁移内皮细胞中的细胞-细胞接触。WR-1065还促进LPS处理的细胞中应力纤维和肌动蛋白细胞骨架形状的保留。因此，LPS在增加[α] 5 [β] 1的顶膜表达和消散应力纤维后扭曲了内皮细胞形态，WR-1065阻止了这种作用。
In septic patients, lipopolysaccharide (LPS) damages the vascular endothelium, which manifests as tissue edema and impaired healing. This pathology occurs when LPS distorts endothelial cell morphology partly by generating free radicals. A radio protector that scavenges free radicals, the aminothiol WR-1065 ([N-2-mercaptoethyl]-1-3-diaminopropane) was found in a prior study to normalize the morphology of irradiated endothelial cells (Mooteri SN, Podolski JL, Drab EA, et al: Radiat Res 145: 217-224, 1996). The aim of this study was to determine whether WR-1065 also normalized endothelial cell morphology following exposure to LPS. For this aim, portions of bovine aortic endothelial cell cultures were denuded and exposed to LPS at 1 ng/mL. After 30 min, the apical membrane expressed increased integrin receptor to fibronectin,[alpha] 5 [beta] 1. After 5 h, the morphology of the cells at the leading edge was distorted, and cell-cell contact was lessened. Also, filamentous actin-containing stress fibers were dissipated; however, filamentous actin content per cell was unchanged. Treatment with 2 mM WR-1065 for 2 h prior to LPS exposure attenuated the increased expression of [alpha] 5 [beta] 1 and promoted cell-cell contact in the migrating endothelial cells. WR-1065 also promoted the retention of stress fibers and actin cytoskeletal shape in cells treated with LPS. Thus, LPS distorted endothelial cell morphology after increasing apical membrance expression of [alpha] 5 [beta] 1 and dissipating stress fibers, effects prevented by WR-1065.