Protein kinase C modulates pulmonary endothelial permeability: a paradigm for acute lung injury.
The intracellular serine/threonine kinase protein kinase C (PKC) has an important role in the genesis of pulmonary edema. This review discusses the PKC-mediated mechanisms that participate in the pulmonary endothelial response to agents involved in lung injury characteristic of the respiratory distress syndrome. Thus the paradigms of PKC-induced lung injury are discussed within the context of pulmonary transvascular fluid exchange. We focus on the signal transduction pathways that are modulated by PKC and their effect on lung endothelial permeability. Specifically, alpha-thrombin, tumor necrosis factor (TNF)-alpha, and reactive oxygen species are discussed because of their well-established roles in both human and experimental lung injury. We conclude that PKC, most likely PKC-alpha, is a primary supporter for lung endothelial injury in response to alpha-thrombin, TNF-alpha, and reactive oxygen species.
Siflinger-Birnboim
Alma
A
Research Service, Stratton Veterans Affairs Medical Center; and the Center for Cardiovascular Science, The Albany Medical College, Albany, New York 12208, USA.
Johnson
Arnold
A
D000818:Animals; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000201:enzymology*; D025461:Feedback, Physiological; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000503:physiopathology*; D010703:Phorbol Esters; D011493:Protein Kinase C / Q000378:metabolism*; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D015398:Signal Transduction; D013917:Thrombin; D014409:Tumor Necrosis Factor-alpha
D010703:Phorbol Esters; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D013917:Thrombin