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• W2110165129 abstract "Purpose of review The protease-antiprotease theory of emphysema is widely accepted, but exactly which cells/proteases play a role continues to be a controversial subject. Recent findings Reports in humans show increased metalloproteinase activity in emphysema, but the exact role of metalloproteinases remains unclear. In laboratory animals, neutrophils turn out to be crucial, and neutrophil influx correlates well with measurements of matrix destruction. Neutrophil influx is linked to metalloproteinase activity, and in mice MMP12-induced release of tumor necrosis factor-α drives neutrophil infiltration. Serine elastase inhibitors, knockout of neutrophil elastase, and interference with tumor necrosis factor-α signaling all provide significant protection against smoke-induced emphysema, but metalloproteinase inhibitors may yield greater protection. In genetically modified mice, emphysema can be produced by overexpression of mediators such as tumor necrosis factor-α, interferon-γ, or interleukin-13, and these models show evidence of metalloproteinase, cysteine protease, and serine protease attack with complicated relationships among these mediators. Collagen breakdown also appears to be important in the genesis of emphysema. Pro-apoptotic agents produce emphysema as well, possibly via an elastolytic pathway. Summary The idea that a single protease or a single type of inflammatory cell is responsible for human emphysema is unlikely to be true; rather, there are complex interactions among proteases, and between proteases and other mediators. The problem at this time is attempting to sort out the numerous candidate effector agents and to determine which of the animal models are relevant to human disease, since there may be considerable discrepancies in the types of proteases and their roles between laboratory animals and humans. There is now good evidence from animal models that antiproteolytic therapy can be of benefit in ameliorating cigarette smoke-induced emphysema." @default.
• W2110165129 created "2016-06-24" @default.
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• W2110165129 date "2005-03-01" @default.
• W2110165129 modified "2023-10-16" @default.
• W2110165129 title "Proteases and emphysema" @default.
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• W2110165129 doi "https://doi.org/10.1097/01.mcp.0000149592.51761.e3" @default.
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