Lung ischemia: endothelial cell signaling by reactive oxygen species. A progress report

These studies using both intact lung and reconstituted cell systems have shown that pulmonary endothelial cells respond rapidly (within several seconds) to the acute cessation of perfusate flow, i.e., ischemia. These effects represent a response to the loss of shear stress and are unrelated to changes in cellular oxygenation. The immediate response is partial depolarization of the endothelial cell membrane followed by activation of endothelial NADPH oxidase and the extracellular generation of superoxide anion. Dismutation of superoxide to H2O2 generates a cell signaling molecule that results in the activation of protein kinases and transcription factors which in turn lead to NO generation and activation of endothelial cell division. The presumed physiological role of this signal cascade is the generation of a vasodilator (NO) and the formation of new capillaries in the effort to restore blood flow.