Early metabolic changes in response to lung injury: extrapolation from animals to humans.

The pulmonary capillary endothelium provides a nonthrombogenic, semipermeable barrier between pulmonary blood and tissues. In recent years, particular attention has been focused on the ability of these cells to metabolize a variety of circulating biologically active substances either by interiorizing the substance through specific membrane transport processes or by directly altering the substance by way of enzymatic activity at the plasma membrane. Serotonin, norepinephrine, and several prostaglandins are examples of biologically active substances that are removed from the circulation by the pulmonary endothelium by way of specific transmembrane transport processes. Concomitant with the increased interest in metabolic functions of the pulmonary endothelium, there has been a growing awareness of the central role of endothelial cell abnormalities in the pathogenesis of various lung injuries and disease states. During the past several years, considerable evidence has accumulated in support of the hypothesis that alterations in the metabolic functions of the lung provide a method of detecting lung injury in vivo, and tests of the metabolic functions of the lung have progressed from in vitro systems to animal models to humans. This paper reviews some of the evidence responsible for this progression and discusses some of the limitations inherent in the extrapolation of lung metabolism studies from animal models to humans. In this discussion, particular emphasis is placed on the pulmonary uptake and metabolism of serotonin, norepinephrine, and prostaglandins E and F by mammalian lungs.