Treatment with Evasin-3 abrogates neutrophil-mediated inflammation in mouse acute pancreatitis
Treatment with Evasin-3 abrogates neutrophil-mediated inflammation in mouse acute pancreatitis
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DOI：
10.1111/eci.12327
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发表时间：
2014-10-01
影响因子：
5.5
通讯作者：
Frossard, Jean-Louis
中科院分区：
文献类型：
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作者：
Montecucco, Fabrizio;Mach, Francois;Frossard, Jean-Louis
背景 急性胰腺炎的特征是炎症过程不仅影响胰腺，还影响肺部。在这里，我们研究了胰腺炎期间肺和胰腺内白细胞浸润和趋化因子表达的时间，以及选择性抑制趋化因子的治疗（使用 Evasins）是否可以改善器官损伤。材料和方法 C57BI/6 小鼠在体内接受 10 小时的雨蛙素腹膜内注射，并随访长达 168 小时。第一次雨蛙素注射后五分钟，腹腔内单次注射10μg Evasin-3、1μg Evasin-4或等体积的载体(PBS)。分别通过免疫组织学和实时RT-PCR评估不同器官中的白细胞、活性氧（ROS）、坏死和趋化因子/细胞因子mRNA表达。结果在肺中，中性粒细胞浸润和巨噬细胞浸润在12小时达到峰值，并伴随CXCL2 mRNA表达增加。与基线相比，24 小时后 CCL2、CXCL1 和 TNF-α 显着增加。没有观察到 CCL3 和 CCL5 的增加。在胰腺中，中性粒细胞浸润在 6 小时达到峰值，而巨噬细胞仅在 72 小时后才增加。 Evasin-3治疗减少了肺中的中性粒细胞浸润、ROS产生和细胞凋亡，并减少了胰腺中的中性粒细胞、巨噬细胞凋亡和坏死。 Evasin-4仅减少肺中的巨噬细胞含量，而在胰腺水平上没有任何益处。结论 胰腺炎期间，肺和胰腺中趋化因子的产生和白细胞浸润得到及时调节。 Evasin-3 抑制 CXC 趋化因子可改善中性粒细胞炎症和损伤，可能会干扰急性胰腺炎和相关肺部并发症的损伤。
Background Acute pancreatitis is characterized by inflammatory processes affecting not only the pancreas, but also the lung. Here, we investigated timing of leucocyte infiltration and chemokine expression within lung and pancreas during pancreatitis and whether treatments selectively inhibiting chemokines (using Evasins) could improve organ injury.Material and methods C57BI/6 mice were submitted in vivo to 10-h intraperitoneal injections of cerulein and followed for up to 168 h. Five minutes after the first cerulein injection, a single intraperitoneal injection of 10 mu g Evasin-3, 1 mu g Evasin-4 or an equal volume of vehicle (PBS) was performed. Leucocytes, reactive oxygen species (ROS), necrosis and chemokine/cytokine mRNA expression were assessed in different organs by immunohistology and real-time RT-PCR, respectively.Results In the lung, neutrophil infiltration and macrophage infiltration peaked at 12 h and were accompanied by increased CXCL2 mRNA expression. CCL2, CXCL1 and TNF-alpha significantly increased after 24 h as compared to baseline. No increase in CCL3 and CCL5 was observed. In the pancreas, neutrophil infiltration peaked at 6 h, while macrophages increased only after 72 h. Treatment with Evasin-3 decreased neutrophil infiltration, ROS production and apoptosis in the lung and reduced neutrophils, macrophages apoptosis and necrosis in the pancreas. Evasin-4 only reduced macrophage content in the lung and did not provide any benefit at the pancreas level.Conclusion Chemokine production and leucocyte infiltration are timely regulated in lung and pancreas during pancreatitis. CXC chemokine inhibition with Evasin-3 improved neutrophil inflammation and injury, potentially interfering with damages in acute pancreatitis and related pulmonary complications.