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Am Rev Respir Dis. 1986 May;133(5):913-27.

Endotoxin and lung injury.


Two things are certain: endotoxin has dramatic effects on the structure and function of the lungs in intact animals and also on isolated lung cells, and both the in vivo and in vitro effects of endotoxin are complex. In whole animals, endotoxin causes obvious and subtle effects on functions of both airways and the pulmonary circulation. These effects include diffuse lung inflammation and injury of pulmonary vascular endothelium. Endotoxin can also directly injure endothelial cells in vitro. In vivo, lung injury caused by endotoxin is at least partly dependent on the presence of granulocytes, and some evidence also suggests that both lymphocytes and macrophages may participate in the response either directly or by directing cell traffic. At least in the sheep preparation, platelets do not seem to play a major role in the lungs' response to endotoxemia. Although endotoxin can activate complement and activated complement infused into whole animals affects the lungs, it seems unlikely that complement activation alone is sufficient to explain the severe and prolonged lung injury caused by endotoxin. Cyclooxygenase metabolites of arachidonic acid appear to mediate both changes in lung mechanics and pulmonary vasoconstriction after endotoxemia. Lipoxygenase products may play a role in these responses as well as the inflammatory response and increases in vascular permeability, although evidence for these latter speculations is not firm. Lung cell injury caused by endotoxin probably is mediated at least in part by generation of free radicals. Inflammatory cells, especially neutrophils, are one source of these toxic oxygen species, but intracellular generation of free radicals within lung cells per se may also be stimulated by endotoxin and account for some of the lung injury. Likewise, inflammatory-cell-derived proteinases may mediate endotoxin-induced injury of lung cells and, as with chronic lung diseases, balance between proteinases and antiproteinases could be important. The fact that free radicals can inactivate antiproteinases, and antiproteinases can act as free radical scavengers, may suggest a complex relationship among the several possible mediators of toxicity. Cyclic nucleotide metabolism is affected in whole animals and isolated lung cells by endotoxin and these classic second messengers could be involved in the pathogenetic sequence, but exactly how is unclear. Chronic effects of endotoxin on the lungs may provide a pathogenetic link between acute lung injury and chronic changes in lung structure and function.(ABSTRACT TRUNCATED AT 400 WORDS)

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