Oncostatin M production by blood and alveolar neutrophils during acute lung injury

Oncostatin M production by blood and alveolar neutrophils during acute lung injury
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DOI:
10.1038/labinvest.3780220
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发表时间:
2001-02-01
影响因子:
5
通讯作者:
Chollet-Martin, S
Chollet-Martin, S
中科院分区:
医学2区
文献类型:
--
作者:
Grenier, A;Combaux, D;Chollet-Martin, S

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中性粒细胞(polymorphisms neutrophil,PMN)参与了急性肺损伤(acute lung injury,ALI)的发病机制,并分泌多种介质,如蛋白酶、活性氧和细胞因子。由于我们最近观察到正常人PMN去活化和合成抑瘤素M(OSM),IL-8家族细胞因子的能力,我们定量OSM生产离体高度纯化的血液和肺泡PMN从24例急性肺损伤患者,包括一些严重的肺炎患者。大多数患者血浆中检测不到OSM,培养的血PMN产生的OSM与健康对照组相似。然而,OSM存在于支气管肺泡灌洗(BAL)液上清液中,在肺炎期间水平显著较高。此外,肺泡OSM水平与通过BAL获得的PMN数量相关,表明PMN是肺泡内OSM的重要来源。事实上,从所有的患者,特别是那些与肺炎,纯化肺泡中性粒细胞强烈产生OSM。有趣的是,在后者患者中,肺泡PMN总是比自体血PMN产生更多的OSM。这些结果通过显示PMN参与肺炎症的调节,证明了PMN在ALI中的功能双重性。
Polymorphonuclear neutrophils (PMN) are involved in the pathogenesis of acute lung injury (ALI), secreting numerous mediators such as proteases, reactive oxygen species, and cytokines. Because we had recently observed the ability of normal human PMN to degranulate and synthesize oncostatin M (OSM), an IL-8-family cytokine, we quantified OSM production ex vivo by highly purified blood and alveolar PMN from 24 ventilated patients with ALI, including some patients with severe pneumonia. Most of the patients had no detectable OSM in plasma, and OSM production by cultured blood PMN was similar to that of healthy controls. However, OSM was present in bronchoalveolar lavage (BAL) fluid supernatant, with significantly higher levels during pneumonia. In addition, alveolar OSM levels correlated with the number of PMN obtained by BAL, suggesting that PMN are an important source of OSM within the alveoli. Indeed, purified alveolar PMN from all of the patients, especially those with pneumonia, strongly produced OSM. Interestingly, in the latter patients, alveolar PMN always produced more OSM than autologous blood PMN. These results document the functional duality of PMN in ALI by showing the participation of PMN in the modulation of lung inflammation.