CHEMOKINE EXPRESSION DURING HEPATIC ISCHEMIA REPERFUSION-INDUCED LUNG INJURY IN THE RAT
CHEMOKINE EXPRESSION DURING HEPATIC ISCHEMIA REPERFUSION-INDUCED LUNG INJURY IN THE RAT
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DOI：
10.1172/jci117630
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发表时间：
1995-01-01
影响因子：
15.9
通讯作者：
STRIETER, RM
中科院分区：
文献类型：
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作者：
COLLETTI, LM;KUNKEL, SL;STRIETER, RM
肝脏对许多病理损伤高度敏感，包括缺血/再灌注损伤。肝损伤的显著后果之一是相关的肺功能障碍，其可能与肝源性细胞因子的释放有关。我们以前采用了肝脏缺血/再灌注损伤的动物模型，并证明这种损伤导致肝源性TNF的产生和释放，其介导嗜中性粒细胞依赖性肺微血管损伤。在这项研究中，我们已经扩展了这些先前的观察结果，以评估TNF和中性粒细胞化学引诱物/活化因子，上皮中性粒细胞活化蛋白-78（ENA-78）之间是否存在相互关系，这可能是该模型中发现的肺损伤病理学的原因。在肝缺血/再灌注损伤的背景下，我们证明了肺病理生理学的以下改变：（a）肺微血管通透性、肺嗜中性粒细胞隔离和肺来源的ENA-78的产生增加;（B）用中和TNF抗血清被动免疫导致肺来源的ENA-78的显著抑制;和（c）用中和ENA-1进行被动免疫78抗血清导致肺中性粒细胞隔离和微血管通透性的显着衰减，类似于我们以前的研究与抗TNF。这些发现支持肺ENA-78响应肝源性TNF产生的概念是肺损伤的重要介质。
The liver is highly susceptible to a number of pathological insults, including ischemia/reperfusion injury. One of the striking consequences of liver injury is the associated pulmonary dysfunction that may be related to the release of hepatic-derived cytokines. We have previously employed an animal model of hepatic ischemia/reperfusion injury, and demonstrated that this injury causes the production and release of hepatic-derived TNF, which mediates a neutrophil-dependent pulmonary microvascular injury. In this study, we have extended these previous observations to assess whether an interrelationship between TNF and the neutrophil chemoattractant/activating factor, epithelial neutrophil activating protein-78 (ENA-78), exists that may be accountable for the pathology of lung injury found in this model, In the context of hepatic ischemia/reperfusion injury, we demonstrated the following alterations in lung pathophysiology: (a) an increase in pulmonary microvascular permeability, lung neutrophil sequestration, and production of pulmonary-derived ENA-78; (b) passive immunization with neutralizing TNF antiserum resulted in a significant suppression of pulmonary-derived ENA-78; and (c) passive immunization with neutralizing ENA-78 antiserum resulted in a significant attenuation of pulmonary neutrophil sequestration and microvascular permeability similar to our previous studies with anti-TNF. These findings support the notion that pulmonary ENA-78 produced in response to hepatic-derived TNF is an important mediator of lung injury.