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.