Alveolar macrophage inducible nitric oxide synthase-dependent pulmonary microvascular endothelial cell septic barrier dysfunction
Alveolar macrophage inducible nitric oxide synthase-dependent pulmonary microvascular endothelial cell septic barrier dysfunction
复制标题
DOI：
10.1016/j.mvr.2008.07.004
复制
发表时间：
2008-11-01
影响因子：
3.1
通讯作者：
Mehta, S.
中科院分区：
文献类型：
--
作者：
Farley, K. S.;Wang, L. F.;Mehta, S.
来自中性粒细胞和肺泡巨噬细胞 (AM) 的诱导型一氧化氮 (NO) 合酶 (iNOS) 有助于小鼠脓毒症急性肺损伤 (ALI) 的病理生理学。目前尚不清楚 AM iNOS 是否对脓毒症肺微血管内皮细胞 (PMVEC) 通透性有直接影响。我们假设 AM iNOS 在脓毒症条件下通过 NO 和过氧亚硝酸盐介导体外 PMVEC 通透性。将细胞培养插入物上的 100,000 个汇合 PMVEC 与 iNOS+/+ 与 iNOS-/- AM 以不同的 AM 与 PMVEC 比例共同孵育。在存在或不存在细胞混合物（等摩尔TNIF-α、IL-1β和IFN-γ）的情况下，通过反式PMVEC伊文思蓝标记的白蛋白流评估PMVEC损伤。细胞混合刺激剂量依赖性地增加反式 PMVEC EB 白蛋白通量，这是夸大的（1.4 +/- 0.1% 与未刺激的 PMVEC 中的 0.4 +/- 0.1%，p
Inducible nitric oxide (NO) synthase (iNOS) from neutrophils and alveolar macrophages (AM) contributes to the pathophysiology of murine septic acute lung injury (ALI). It is not known if AM iNOS has a direct effect on septic pulmonary microvascular endothelial cell (PMVEC) permeability. We hypothesized that AM iNOS mediates PMVEC permeability in vitro under septic conditions through NO and peroxynitrite. 100,000 confluent PMVEC on cell-culture inserts were co-incubated with iNOS+/+ vs. iNOS-/- AM, in various ratios of AM to PMVEC. PMVEC injury was assessed by trans-PMVEC Evans Blue-labelled albumin flux in the presence or absence of cytomix (equimolar TNIF-alpha, IL-1 beta and IFN-gamma). Cytomix stimulation dose-dependently increased trans-PMVEC EB-albumin flux, which was exaggerated (1.4 +/- 0.1% vs. 0.4 +/- 0.1% in unstimulated PMVEC, p