Treatment with antileukinate, a CXCR2 chemokine receptor antagonist, protects mice against acute pancreatitis and associated lung injury
Treatment with antileukinate, a CXCR2 chemokine receptor antagonist, protects mice against acute pancreatitis and associated lung injury
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DOI：
10.1016/j.regpep.2006.08.006
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发表时间：
2007-01-10
影响因子：
--
通讯作者：
Hegde, Akhil
中科院分区：
文献类型：
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作者：
Bhatia, Madhav;Hegde, Akhil
急性胰腺炎是一种常见且目前无法治愈的临床疾病，近年来其发病率不断上升。趋化因子被认为在急性胰腺炎的发病机制中起关键作用。我们先前已表明，用一种针对细胞因子诱导的中性粒细胞趋化因子（CINC，一种CXC趋化因子）的中和抗体进行治疗，可保护大鼠免受急性胰腺炎相关的肺损伤。六肽抗白细胞素（Ac - RRWWCR - NH₂）是CXC趋化因子与受体（CXCR2）结合的强效抑制剂。本研究旨在评估抗白细胞素治疗对小鼠急性胰腺炎及相关肺损伤的影响。通过每小时腹腔注射雨蛙肽（50μg/kg/h），持续10小时，在成年雄性瑞士小鼠中诱导急性胰腺炎。在开始注射雨蛙肽前30分钟或1小时后，给小鼠皮下注射抗白细胞素（52.63mg/kg）。通过测量血浆淀粉酶、胰腺含水量、胰腺髓过氧化物酶（MPO）活性、胰腺巨噬细胞炎性蛋白 - 2（MIP - 2）水平以及对胰腺切片进行组织学检查来确定急性胰腺炎的严重程度。将肺MPO活性升高以及肺切片中肺损伤的组织学证据作为胰腺炎相关肺损伤的标准。抗白细胞素治疗可保护小鼠免受急性胰腺炎及相关肺损伤，从而表明抗趋化因子疗法在这种疾病中可能有价值。（c）2006爱思唯尔公司。版权所有。
Acute pancreatitis is a common, and as yet incurable, clinical condition, the incidence of which has been increasing over recent years. Chemokines are believed to play a key role in the pathogenesis of acute pancreatitis. We have earlier shown that treatment with a neutralizing antibody against CINC, a CXC chemokine, protects rats against acute pancreatitis-associated lung injury. The hexapeptide antileukinate (Ac-RRWWCR-NH2) is a potent inhibitor of binding of CXC chemokines to the receptors (CXCR2). This study aims to evaluate the effect of treatment with antileukinate on acute pancreatitis and the associated lung injury in mice. Acute pancreatitis was induced in adult male Swiss mice by hourly intra-peritoneal injections of caerulein (50 mu g/kg/h) for 10 h. Antileukinate (52.63 mg/kg, s.c.) was administered to mice either 30 min before or I h after starting caerulein injections. Severity of acute pancreatitis was determined by measuring plasma amylase, pancreatic water content, pancreatic myeloperoxidase (MPO) activity, pancreatic macrophage inflammatory protein-2 (MIP-2) levels and histological examination of sections of pancreas. A rise in lung MPO activity and histological evidence of lung injury in lung sections was used as criteria for pancreatitis-associated lung injury. Treatment with antileukinate protected mice against acute pancreatitis and associated lung injury, showing thereby that antichemokine therapy may be of value in this condition. (c) 2006 Elsevier B.V. All rights reserved.