Kashiwagi M, Friess H, Uhl W, Graber H, Duarte R, Zimmermann A, Büchler M W
Department of Visceral and Transplantation Surgery, University of Bern, Switzerland.
Ann Surg. 1998 Feb;227(2):220-8. doi: 10.1097/00000658-199802000-00011.
To determine if phospholipase A2 (PLA2) type II and type IV mRNA expression and protein are altered in chronic pancreatitis.
PLA2s have an important regulatory function in several signaling pathways, especially in inflammation. In this study, we examined the expression of three PLA2 isoforms (type I, type II, and type IV) in chronic pancreatitis.
The distribution of PLA2 was studied in 15 pancreas samples obtained from patients with chronic pancreatitis using immunohistochemical, Northern blot, and in situ hybridization techniques. Normal pancreas obtained from healthy organ donors served as control.
Northern blot analysis revealed enhanced mRNA levels of PLA2 type II (5.7-fold) and type IV (5.1-fold) in chronic pancreatitis (p < 0.01) versus normal pancreas. In normal pancreas, intense PLA2 type I immunostaining was present in acinar cells, whereas PLA2 type II immunostaining was visible only in some acinar cells. In chronic pancreatitis, PLA2 type II immunostaining was present more frequently and with higher intensity in acinar cells. Furthermore, PLA2 type II immunoreactivity was more abundant in metaplastic ductal cells in the chronic pancreatitis samples. By in situ hybridization, areas with ductal metaplasia in chronic pancreatitis exhibited intense PLA2 type IV mRNA signals. All chronic pancreatitis tissues with concomitantly increased mRNA expression for PLA2 type II and type IV exhibited a higher degree of degeneration, ductal metaplasia, and fibrosis.
Upregulation of PLA2 types II and IV in areas with more histologic damage suggests that these PLA2 isoforms might contribute to the morphologic changes that occur in chronic pancreatitis.
确定II型和IV型磷脂酶A2(PLA2)的mRNA表达及蛋白在慢性胰腺炎中是否发生改变。
PLA2在多种信号通路尤其是炎症中具有重要的调节功能。在本研究中,我们检测了三种PLA2亚型(I型、II型和IV型)在慢性胰腺炎中的表达。
采用免疫组织化学、Northern印迹和原位杂交技术,对15例慢性胰腺炎患者的胰腺样本中PLA2的分布进行研究。取自健康器官供体的正常胰腺作为对照。
Northern印迹分析显示,与正常胰腺相比,慢性胰腺炎中PLA2 II型(5.7倍)和IV型(5.1倍)的mRNA水平升高(p < 0.01)。在正常胰腺中,腺泡细胞存在强烈的PLA2 I型免疫染色,而PLA2 II型免疫染色仅在部分腺泡细胞中可见。在慢性胰腺炎中,腺泡细胞中PLA2 II型免疫染色更频繁且强度更高。此外,慢性胰腺炎样本中化生的导管细胞中PLA2 II型免疫反应性更丰富。通过原位杂交,慢性胰腺炎中出现导管化生的区域呈现强烈的PLA2 IV型mRNA信号。所有PLA2 II型和IV型mRNA表达同时增加的慢性胰腺炎组织均表现出更高程度的变性、导管化生和纤维化。
在组织损伤更严重的区域,PLA2 II型和IV型上调表明这些PLA2亚型可能促成了慢性胰腺炎中发生的形态学改变。