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首页> 外文期刊>American Journal of Physiology >In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury.
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In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury.

机译：体内证据表明GM-CSF在急性胰腺炎相关性肺损伤中作为介质发挥作用。

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摘要

Severe pancreatitis is frequently associated with acute lung injury (ALI) and the respiratory distress syndrome. The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mediating the ALI associated with secretagogue-induced experimental pancreatitis was evaluated with GM-CSF knockout mice (GM-CSF -/-). Pancreatitis was induced by hourly (12x) intraperitoneal injection of a supramaximally stimulating dose of the cholecystokinin analog caerulein. The resulting pancreatitis was similar in GM-CSF-sufficient (GM-CSF +/+) control animals and GM-CSF -/- mice. Lung injury, quantitated by measuring lung myeloperoxidase activity (an indicator of neutrophil sequestration), alveolar-capillary permeability, and alveolar membrane thickness was less severe in GM-CSF -/- than in GM-CSF +/+ mice. In GM-CSF +/+ mice, pancreas, lung and serum GM-CSF levels increase during pancreatitis. Lung levels of macrophage inflammatory protein (MIP)-2 are also increased during pancreatitis, but, in this case, the rise is less profound in GM-CSF -/- mice than in GM-CSF +/+ controls. Administration of anti-MIP-2 antibodies was found to reduce the severity of pancreatitis-associated ALI. Our findings indicate that GM-CSF plays a critical role in coupling pancreatitis to ALI and suggest that GM-CSF may act indirectly by regulating the release of other proinflammatory factors including MIP-2.
机译：严重的胰腺炎通常与急性肺损伤（ALI）和呼吸窘迫综合征相关。用GM-CSF敲除小鼠（GM-CSF-/-）评估了粒细胞巨噬细胞集落刺激因子（GM-CSF）在介导与促分泌素诱导的实验性胰腺炎相关的ALI中的作用。每小时（12次）腹腔内注射超最大刺激剂量的胆囊收缩素类似物caerulein诱发胰腺炎。在足够GM-CSF（GM-CSF + / +）对照动物和GM-CSF-/-小鼠中，所得的胰腺炎相似。通过测量肺髓过氧化物酶活性（中性粒细胞螯合的指标），肺泡-毛细血管通透性和肺泡膜厚度的量化，与GM-CSF + / +小鼠相比，肺损伤不那么严重。在GM-CSF + / +小鼠中，胰腺炎期间胰腺，肺和血清GM-CSF水平升高。胰腺炎期间，巨噬细胞炎性蛋白（MIP）-2的肺水平也增加，但在这种情况下，GM-CSF-/-小鼠的升高不如GM-CSF + / +对照高。发现给予抗MIP-2抗体可降低胰腺炎相关ALI的严重程度。我们的发现表明，GM-CSF在将胰腺炎与ALI偶联中起关键作用，并提示GM-CSF可能通过调节包括MIP-2在内的其他促炎因子的释放而间接发挥作用。

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