STUDY OF ADHESION MOLECULES, CYTOSKELETON AND SIGNAL TRANSDUCTION PATHWAY ON INJURY OF ENDOTHELIAL CELLS FOR ISOLATED PRESERVED LUNGS

点击翻译按钮获取中文摘要

We showed that neutrophils-induced lung injury was induced by reactive oxygen species generated via xanthine oxidase (XO) following adhesion of neutrophils on the endothelial cells. Usually, XO does not exist in the neutrophils but endothelial cells. Therefore we speculate if this kind of lung injury is induced by activation of endothelial cells themselves. In the experiments of isolated perfused rat lungs, whether intracellular signal transduction systems were involved in the injury of the pulmonary vascular endothelial cells caused by activated neutrophils, we investigated using a protein kinase C antagonist. We showed that PKC antagonist ameliorated the pulmonary vascular injury caused by activated neutrophils in a dose dependent manner. Moreover, we showed that the pulmonary vascular permeability was increased by a PKC agonist without neutrophils. On the other hand, in cell culture models, it was impossible to measure protein permeability for cell culture sheets, we measured trans- … More endothelial electrical resistance (TER) across the cultured pulmonary vascular endothelial cell sheets. We continuously measured TER of the cultured cell sheets from rat pulmonary vascular endothelial cells when they were confluent and the tested the several kinds of agonists and antagonists to the cultured cell sheets. The TERs of the cultured cell sheets were decreased by PKC agonists by dose dependent manner, meanwhile DMSO, a vehicle of PKC agonist, failed. These findings supported the results from the experiment of isolated rat lungs. We also stained actin fibers in the pulmonary vascular endothelial cells. Actin fibers existed at the peripheral area of the cytosol without any stimulations, however, they were depolymerized and moved around nucleus by PKC agonist. These findings suggest that the pulmonary vascular endothelial cells were changed their morphology by depolymerizing actin fibers by PKC when they were activated by some stimulations, and finally pulmonary microvascular permeability was increased. Less