Grau G E, Mili N, Lou J N, Morel D R, Ricou B, Lucas R, Suter P M
Department of Anaesthesiology, University Hospital, Geneva, Switzerland.
Lab Invest. 1996 Apr;74(4):761-70.
The purpose of this study was to assess the phenotypic and functional characteristics of pulmonary microvascular endothelial cells (MVEC) in the acute respiratory distress syndrome (ARDS). Pulmonary MVEC were isolated from the lungs of five patients who developed ARDS, and from four patients who had undergone a lobectomy for lung carcinoma, as controls. Adhesion molecules and other surface molecules were quantitated on these cells by flow cytometry and the cytokines IL-6 and IL-8 were measured in the supernatants by ELISA. The constitutive expression of intercellular adhesion molecule and, to a lesser extent, vascular adhesion molecule-1, was significantly increased on MVEC isolated from all ARDS patients, as compared with control MVEC. CD14 and TNF receptor p75 were also increased on the surface of MVEC isolated from most patients with ARDS. The expression of ELAM-1 and TNF receptor p55 (TNF-R1) was not significant on the surface of either ARDS-derived or control pulmonary MVEC. The constitutive ability of ARDS-derived MVEC to secrete IL-6 and IL-8 was markedly enhanced as compared with control MVEC. Upon in vitro restimulation by TNF, pulmonary MVEC from ARDS patients showed lower ICAM-1 upregulation, but similar IL-6 and IL-8 production capacity, when compared with control MVEC. Selective differences were found in cell adhesion molecules and TNF receptor p75 expression on pulmonary MVEC isolated from patients with ARDS. These pulmonary MVEC spontaneously overexpress some adhesion molecules and produce greater amounts of the pro- and anti-inflammatory cytokines IL-8 and IL-6. These findings suggest that ICAM-1 and TNF receptor p75 may have a particular involvement in the pathogenesis of acute lung injury, and that the endothelium may be an important source of cytokines detected in broncho-alveolar lavage during this syndrome. It is tempting to hypothesize that the differences observed result from either a genetic predisposition to ARDS based on MVEC phenotype or to a long-lived MVEC phenotypic change induced by ARDS. By allowing the monitoring of phenotypic and functional parameters, cultures of pulmonary MVEC isolated from ARDS patients may thus represent a useful system to analyze further the mechanisms of acute lung injury and to evaluate the efficacy of drugs, including inhibitors of cytokines and of adhesion molecules.
本研究的目的是评估急性呼吸窘迫综合征（ARDS）中肺微血管内皮细胞（MVEC）的表型和功能特征。从5例发生ARDS的患者以及4例因肺癌接受肺叶切除术的患者（作为对照）的肺中分离出肺MVEC。通过流式细胞术对这些细胞上的黏附分子和其他表面分子进行定量，并通过ELISA法测定上清液中的细胞因子IL-6和IL-8。与对照MVEC相比，从所有ARDS患者分离出的MVEC上细胞间黏附分子以及程度较轻的血管黏附分子-1的组成性表达显著增加。大多数ARDS患者分离出的MVEC表面上的CD14和TNF受体p75也增加。ELAM-1和TNF受体p55（TNF-R1）在ARDS来源的或对照肺MVEC表面上的表达均不显著。与对照MVEC相比，ARDS来源的MVEC分泌IL-6和IL-8的组成性能力明显增强。在体外经TNF再刺激后，与对照MVEC相比，ARDS患者的肺MVEC显示出较低的ICAM-1上调，但IL-6和IL-8产生能力相似。在从ARDS患者分离出的肺MVEC上的细胞黏附分子和TNF受体p75表达中发现了选择性差异。这些肺MVEC自发地过度表达一些黏附分子，并产生大量促炎和抗炎细胞因子IL-8和IL-6。这些发现表明，ICAM-1和TNF受体p75可能特别参与急性肺损伤的发病机制，并且内皮细胞可能是该综合征期间支气管肺泡灌洗中检测到的细胞因子的重要来源。很容易推测，观察到的差异是由于基于MVEC表型的ARDS遗传易感性或由ARDS诱导的长期MVEC表型变化所致。通过监测表型和功能参数，从ARDS患者分离出的肺MVEC培养物可能因此代表一个有用的系统，用于进一步分析急性肺损伤的机制并评估药物的疗效，包括细胞因子和黏附分子抑制剂。
