Interaction of complement and leukocytes in severe acute pancreatitis:: potential for therapeutic intervention
Interaction of complement and leukocytes in severe acute pancreatitis:: potential for therapeutic intervention
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DOI：
10.1152/ajpgi.00016.2006
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发表时间：
2006-11-01
影响因子：
4.5
通讯作者：
Werner, Jens
中科院分区：
文献类型：
--
作者：
Hartwig, Werner;Klafs, Martina;Werner, Jens
在急性胰腺炎中，局部以及全身器官并发症由各种炎症级联反应的激活介导。补体在这种情况下的作用尚不清楚。本研究的目的是确定实验性胰腺炎中补体激活的水平，以评估补体和白细胞-内皮细胞激活的相互作用，并评估可溶性补体受体1（sCR 1）在这种情况下抑制补体的作用。坏死性胰腺炎诱导在Wistar大鼠的结合静脉雨蛙肽和逆行灌注glycodeoxycholic acid到胆胰管;水肿性胰腺炎诱导静脉雨蛙肽。在对照动物中，进行假手术（中线剖腹术）。在存在/不存在sCR 1的情况下评估补体激活、白细胞隔离和胰腺以及肺损伤。C3 a水平升高见于坏死性胰腺炎，而水肿性胰腺炎则无。当坏死性胰腺炎中的补体激活被sCR 1阻断时，C3 a和总溶血活性（CH 50）水平降低。通过活体显微镜检查评估的白细胞-内皮相互作用以及胰腺和肺器官损伤（湿干重比、MPO活性和组织学）均通过sCR 1得到改善。作为本研究的结果，坏死性胰腺炎而非水肿性胰腺炎的特征是显著的和早期的补体激活。基于补体与白细胞的相互作用，sCR 1抑制补体可能是治疗重症胰腺炎中白细胞相关器官损伤的一种有价值的选择。
In acute pancreatitis, local as well as systemic organ complications are mediated by the activation of various inflammatory cascades. The role of complement in this setting is unclear. The aim of the present study was to determine the level of complement activation in experimental pancreatitis, to evaluate the interaction of complement and leukocyte-endothelium activation, and to assess the effects of complement inhibition by soluble complement receptor 1 (sCR1) in this setting. Necrotizing pancreatitis was induced in Wistar rats by the combination of intravenous cerulein and retrograde infusion of glycodeoxycholic acid into the biliopancreatic duct; edematous pancreatitis was induced by intravenous cerulein only. In control animals, a sham operation (midline laparotomy) was performed. Complement activation, leukocyte sequestration, and pancreatic as well as pulmonary injury were assessed in the presence/absence of sCR1. Increased levels of C3a were found in necrotizing but not in edematous pancreatitis. When complement activation in necrotizing pancreatitis was blocked by sCR1, levels of C3a and total hemolytic activity (CH50) were decreased. Leukocyte-endothelial interaction, as assessed by intravital microscopy, and pancreatic as well as pulmonary organ injury (wet-to-dry weight ratio, MPO activity, and histology) were ameliorated by sCR1. As a result of the present study, necrotizing but not edematous pancreatitis is characterized by significant and early complement activation. Based on the interaction of complement and leukocytes, complement inhibition by sCR1 may be a valuable option in the treatment of leukocyte-associated organ injury in severe pancreatitis.