Clinical application of evaluation of complement protein levels in the exocrine pancreas to determine the pancreatic disease activity

补体系统是正常免疫和炎症反应的有效效应子。微生物的侵入，结合十二指肠内容物的反流，可能是急性和慢性胰腺炎发病机制的重要因素。然而，胰腺外分泌系统的免疫保护机制尚不清楚，分泌型伊加系统已被证实存在于胰液中。此外，我们发现几种补体蛋白被分泌到胰液中。从我们的结果来看，补体C3、C4和B因子以高浓度存在于胰液中。此外，几种胰腺癌细胞系响应于IL-1β、TNF-α和IFN-γ而分泌这些补体蛋白，这表明导管上皮细胞是补体蛋白的可能生物合成位点。我们还试图检测补体mRNA的表达原位。虽然在胰腺组织中的原位杂交是困难的，我们检测到一些样品中的补体mRNA的表达。此外，我们在一些慢性胰腺炎样本中观察到高mRNA表达。当比较正常和慢性胰腺炎之间的胰液中的补体水平时，我们在慢性胰腺炎样品中检测到大量的C3。因此，我们的研究提出了一种可能性，即测定胰液中的补体蛋白有助于评估疾病的活动性，如慢性胰腺炎。

The complement system is a potent effector of the normal immune and inflammatory responses. Invasion by microorganisms, combined with a reflux of duodenal contents, may be important factors in the pathogenesis of acute and chronic pancreatitis. However, little is known about the mechanism underlying the immunologic protection of the exocrine pancreas.The secretory IgA system has been shown to be present in pancreatic fluids. In addition, we found that several complement proteins are secreted into pancreatic juices. From our results, complement C3, C4 and factor B are present in pancreatic juice at high concentration. Furthermore, several pancreatic cancer cell lines are secreting these complement proteins in responses to IL-1β, TNF-α and IFN-γ suggesting that ductal epithelial cells are possible biosynthetic site of complement proteins. We also tried to detect complement mRNA expression in situ. Although in situ hybridization in the pancreatic tissue is difficult, we detected complement mRNA expression in some samples. In addition, we observed high mRNA expression in some samples of chronic pancreatitis. When comparing the complement levels in pancreatic juices between normal and chronic pancreatitis, we detect high amounts of C3 in samples of chronic pancreatitis. Thus, our investigation presented a possibility that determination of complement proteins in pancreatic juices is useful to evaluate disease activity, such as chronic pancreatitis.