The Annals of thoracic surgery
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Functional roles of tumor necrosis factor-alpha and interleukin 1-Beta in hypoxia and reoxygenation.
Intercellular signaling plays an important role in the development of lung ischemia-reperfusion injury. However, the role of specific mediators remains poorly characterized. Alveolar macrophages (AM) produce soluble mediators early in reperfusion, which modulate the responses of endothelial and epithelial cells to oxidative stress. There is a burst of proinflammatory cytokine production in a variety of cells; however, interleukin 1-beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) localize to the AM. We hypothesized that these cytokines account for the costimulatory effects that AM exert on endothelial and epithelial cells. ⋯ Interleukin 1-beta and TNF-α are critical mediators in the intercellular communication pathways that allow the AM to enhance the response of surrounding cells to oxidative stress.
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Toll-like receptor-4 has been implicated in modulating ischemia-reperfusion injury in cardiac, hepatic, renal, and cerebral models. However, its role in lung ischemia-reperfusion injury is unknown. We hypothesize that toll-like receptor-4 has a key role in initiating the inflammatory cascade in lung ischemia-reperfusion injury. ⋯ Toll-like receptor-4 is critical in the development of lung ischemia-reperfusion injury and its activation in the alveolar macrophage may be the initiating step.