Vonlaufen A, Aurrand-Lions M, Pastor C M, Lamagna C, Hadengue A, Imhof B A, Frossard J-L
Division of Gastroenterology, Department of Internal Medicine, University Hospitals, Geneva, Switzerland.
J Pathol. 2006 Aug;209(4):540-8. doi: 10.1002/path.2007.
The recruitment of inflammatory cells contributes significantly to tissue injury in acute pancreatitis. This process implies several molecular interactions between circulating and endothelial cells. The adhesion molecule junctional adhesion molecule C (JAM-C) is involved in leukocyte transendothelial migration and it can form homophilic (JAM-C/JAM-C) and heterophilic interactions with the leukocyte integrin alpha(M)beta(2). In this study, the effect of early administration of monoclonal antibodies directed against JAM-C in cerulein-induced acute pancreatitis was assessed. This reagent significantly blocked influx of leukocytes, release of serum amylase, secretion of inflammatory cytokines, and acinar cell necrosis. These effects were rapid and protected against tissue injury throughout the duration of the model. Conversely, cerulein-induced acute pancreatitis was more severe in transgenic mice overexpressing JAM-C on endothelial cells under the control of the Tie2 promoter. It is proposed that JAM-C expressed by endothelial cells contributes to the pathophysiology of acute pancreatitis and could be considered a target for clinical applications.
炎症细胞的募集在急性胰腺炎的组织损伤中起重要作用。这一过程涉及循环细胞与内皮细胞之间的多种分子相互作用。黏附分子连接黏附分子C（JAM-C）参与白细胞跨内皮迁移，它可与白细胞整合素α(M)β(2)形成同源（JAM-C/JAM-C）和异源相互作用。在本研究中，评估了早期给予抗JAM-C单克隆抗体对雨蛙肽诱导的急性胰腺炎的影响。该试剂显著阻断白细胞流入、血清淀粉酶释放、炎性细胞因子分泌以及腺泡细胞坏死。这些作用迅速，且在整个模型持续期间都能保护组织免受损伤。相反，在Tie2启动子控制下内皮细胞过度表达JAM-C的转基因小鼠中，雨蛙肽诱导的急性胰腺炎更为严重。有人提出，内皮细胞表达的JAM-C促成急性胰腺炎的病理生理学，可被视为临床应用的一个靶点。
