Intracellular rupture, exocytosis and actin interaction of endocytic vacuoles in pancreatic acinar cells: initiating events in acute pancreatitis.
Intracellular rupture, exocytosis and actin interaction of endocytic vacuoles in pancreatic acinar cells: initiating events in acute pancreatitis.
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DOI：
10.1113/jp275879
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Tepikin AV
中科院分区：
文献类型：
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作者：
Chvanov M;De Faveri F;Moore D;Sherwood MW;Awais M;Voronina S;Sutton R;Criddle DN;Haynes L;Tepikin AV
在急性胰腺炎诱导剂的刺激下，胰腺腺泡细胞内形成巨大的含有胰蛋白酶的内吞液泡。F -肌动蛋白包膜内吞液泡并调节其性质。内吞液泡可以破裂并将其内容物释放到腺泡细胞的细胞质中。内吞液泡可以与腺泡细胞质膜融合，并将其内容物排出体外。胰蛋白酶原的胰腺内活化是急性胰腺炎发展的早期事件和标志。内吞液泡是由大的胞后结构的断开和运输形成的，是活胰腺腺泡细胞中胰蛋白酶活性的唯一可解析位点。在本研究中，我们描述了生理和病理生理刺激诱导的内吞液泡形成的动力学，并看到了一个完全或部分包围内吞液泡的突出的肌动蛋白外壳。急性胰腺炎诱导剂牛磺酸胆酸3‐硫酸和超高浓度的胆囊收缩素触发巨大（直径大于2.5 μm）内吞液泡的形成。我们发现并描述了细胞内的内吞液泡破裂以及内吞液泡与质膜基部和根尖区域的融合。用特异性蛋白酶抑制剂进行的实验表明，内吞液泡的破裂可能不是由胰蛋白酶或组织蛋白酶b引起的。液泡周围丝状肌动蛋白（在约30%的内吞液泡表面观察到）可能通过防止液泡破裂和液泡与质膜融合而起稳定作用。内吞液泡的破裂和融合使胰蛋白酶能够摆脱膜限制细胞器的限制，进入细胞内和细胞外靶标，并启动胰腺的自消化，这是一个重要的病理生理事件。在急性胰腺炎诱导剂的刺激下，胰腺腺泡细胞内形成巨大的含有胰蛋白酶的内吞液泡。F -肌动蛋白包膜内吞液泡并调节其性质。内吞液泡可以破裂并将其内容物释放到腺泡细胞的细胞质中。内吞液泡可以与腺泡细胞质膜融合，并将其内容物排出体外。
Giant trypsin‐containing endocytic vacuoles are formed in pancreatic acinar cells stimulated with inducers of acute pancreatitis. F‐actin envelops endocytic vacuoles and regulates their properties. Endocytic vacuoles can rupture and release their content into the cytosol of acinar cells. Endocytic vacuoles can fuse with the plasma membrane of acinar cells and exocytose their content. Intrapancreatic activation of trypsinogen is an early event in and hallmark of the development of acute pancreatitis. Endocytic vacuoles, which form by disconnection and transport of large post‐exocytic structures, are the only resolvable sites of the trypsin activity in live pancreatic acinar cells. In the present study, we characterized the dynamics of endocytic vacuole formation induced by physiological and pathophysiological stimuli and visualized a prominent actin coat that completely or partially surrounded endocytic vacuoles. An inducer of acute pancreatitis taurolithocholic acid 3‐sulphate and supramaximal concentrations of cholecystokinin triggered the formation of giant (more than 2.5 μm in diameter) endocytic vacuoles. We discovered and characterized the intracellular rupture of endocytic vacuoles and the fusion of endocytic vacuoles with basal and apical regions of the plasma membrane. Experiments with specific protease inhibitors suggest that the rupture of endocytic vacuoles is probably not induced by trypsin or cathepsin B. Perivacuolar filamentous actin (observed on the surface of ∼30% of endocytic vacuoles) may play a stabilizing role by preventing rupture of the vacuoles and fusion of the vacuoles with the plasma membrane. The rupture and fusion of endocytic vacuoles allow trypsin to escape the confinement of a membrane‐limited organelle, gain access to intracellular and extracellular targets, and initiate autodigestion of the pancreas, comprising a crucial pathophysiological event. Giant trypsin‐containing endocytic vacuoles are formed in pancreatic acinar cells stimulated with inducers of acute pancreatitis. F‐actin envelops endocytic vacuoles and regulates their properties. Endocytic vacuoles can rupture and release their content into the cytosol of acinar cells. Endocytic vacuoles can fuse with the plasma membrane of acinar cells and exocytose their content.