Role for macrophage migration inhibitory factor in acute respiratory distress syndrome
Role for macrophage migration inhibitory factor in acute respiratory distress syndrome
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DOI：
10.1002/path.1291
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发表时间：
2003-04-01
影响因子：
7.3
通讯作者：
Lan, HY
中科院分区：
文献类型：
--
作者：
Lai, KN;Leung, JCK;Lan, HY
巨噬细胞移动抑制因子（MIF）在急性呼吸窘迫综合征（ARDS）炎症性肺损伤中的重要作用近年来被提出。本研究证实了在ARDS患者肺泡毛细血管内皮细胞和肺组织浸润的巨噬细胞中MIF蛋白表达增强。使用用MIF刺激的培养的内皮细胞和脂多糖（LPS）诱导的急性肺损伤的小鼠模型测试MIF在ARDS中以自分泌方式上调其合成的可能性。MIF诱导显着的MIF和肿瘤坏死因子（TNF）-α的合成在培养的内皮细胞和中和抗MIF抗体的效果被阻断。当用中和性抗TNF-α抗体或糖皮质激素预处理MIF刺激的内皮细胞时，观察到类似的阻断作用，支持MIF通过放大促炎环诱导TNF-α产生的观点。在LPS诱导的急性肺损伤小鼠中，抗MIF或糖皮质激素治疗有效地减轻了肺病理学和MIF或TNF-α的合成。ARDS时肺泡毛细血管内皮细胞水通道蛋白1（AQP 1）表达轻度增强。体外研究表明，MIF和TNF-α都诱导培养的内皮细胞中AQP 1合成的小幅增加。这些结果表明，MIF在导致ARDS的肺泡炎症中起着重要的病理作用。抗MIF和早期糖皮质激素治疗可能是减少ARDS肺泡炎症的一种新的治疗方法。版权所有（C）2003约翰威利父子有限公司。
The critical role of macrophage migration inhibitory factor (MIF) in mediating inflammatory lung injury in acute respiratory distress syndrome (ARDS) has been raised recently. The present study has identified enhanced MIF protein expression in alveolar capillary endothelium and infiltrating macrophages in lung tissues from ARDS patients. The possibility that MIF up-regulates its synthesis in an autocrine fashion in ARDS was tested using cultured endothelial cells stimulated with MIF and a murine model of lipopolysaccharide (LPS)-induced acute lung injury. MIF induced significant MIF and tumour necrosis factor (TNF)-alpha synthesis in cultured endothelial cells and the effect was blocked by neutralizing anti-MIF antibody. A similar blocking effect was observed when MIF-stimulated endothelial cells were pretreated with neutralizing anti-TNF-alpha antibody or glucocorticoid, supporting the notion that MIF induced TNF-alpha production via an amplifying pro-inflammatory loop. Treatment with anti-MIF or glucocorticoid effectively attenuated pulmonary pathology and the synthesis of MIF or TNF-alpha in mice with LPS-induced acute lung injury. Mildly augmented expression of aquaporin 1 (AQP1) was also detected in alveolar capillary endothelium in ARDS. In vitro studies revealed that both MIF and TNF-alpha induced a small increase of AQP1 synthesis in cultured endothelial cells. These findings suggest that MIF plays a crucial pathological role leading to alveolar inflammation in ARDS. Anti-MIF and early glucocorticoid therapy may represent a novel therapeutic approach for reducing alveolar inflammation in ARDS. Copyright (C) 2003 John Wiley Sons, Ltd.