Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury.
Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury.
复制标题
JAM-C 调节的反向迁移中性粒细胞参与急性胰腺炎相关肺损伤。
DOI：
10.1038/srep20545
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发表时间：
2016-02-04
影响因子：
4.6
通讯作者：
Hu G
中科院分区：
文献类型：
--
作者：
Wu D;Zeng Y;Fan Y;Wu J;Mulatibieke T;Ni J;Yu G;Wan R;Wang X;Hu G
连接粘附分子- c （JAM-C）在促进中性粒细胞的反向跨内皮迁移（rTEM）中起关键作用，这有助于全身炎症的传播和继发性器官损伤。急性胰腺炎（AP）期间，全身炎症反应导致远端器官损伤，通常导致急性肺损伤（ALI）。在这里，我们研究了rTEM中性粒细胞在ap相关ALI中的作用，以及JAM-C在这种疾病中调节中性粒细胞rTEM的分子机制。本研究发现，小鼠急性肺损伤模型和人急性肺损伤患者外周血中均存在rTEM中性粒细胞，且随肺损伤严重程度的增加而升高。小鼠实验性胰腺炎期间胰腺JAM-C表达下调，其表达水平与中性粒细胞rTEM升高和肺损伤严重程度呈负相关。敲除JAM-C导致更严重的肺损伤和全身性炎症。JAM-C敲除的AP小鼠的循环和肺血管冲洗中均存在大量的rTEM中性粒细胞。本研究表明，在AP期间，被募集到胰腺的中性粒细胞可能会迁移回循环，然后促进ALI。JAM-C下调可能通过促进中性粒细胞rTEM促进ap相关的ALI。
Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM.