Lasting inhibition of receptor-mediated calcium oscillations in pancreatic acini by neutrophil respiratory burst - A novel mechanism for secretory blockade in acute pancreatitis?
Lasting inhibition of receptor-mediated calcium oscillations in pancreatic acini by neutrophil respiratory burst - A novel mechanism for secretory blockade in acute pancreatitis?
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中性粒细胞呼吸爆发对胰腺腺泡中受体介导的钙振荡的持久抑制——急性胰腺炎分泌阻断的新机制？
DOI：
10.1016/j.bbrc.2013.06.081
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发表时间：
2013-08-02
影响因子：
3.1
通讯作者：
Cui, Zong Jie
中科院分区：
文献类型：
--
作者：
Liang, Hui Yuan;Song, Zhi Min;Cui, Zong Jie
虽然大量证据表明中性粒细胞浸润是急性胰腺炎的早期事件，但中性粒细胞呼吸爆发对胰腺腺泡的影响尚未研究。在本工作中，检查了fMLP诱导的中性粒细胞呼吸爆发对胰腺腺泡的影响。发现中性粒细胞呼吸爆发阻断胆囊收缩素或乙酰胆碱引起的钙振荡。这种持久的抑制作用取决于爆发的中性粒细胞的密度，并且可以通过增加激动剂浓度来克服。在AR 4 - 2 J细胞中也观察到胆囊收缩素刺激的抑制。与此形成鲜明对比的是，中性粒细胞呼吸爆发对苯肾上腺素（PE）、加压素或ATP诱导的大鼠肝细胞钙振荡没有影响。这些数据共同表明，中性粒细胞呼吸爆发抑制胰腺腺泡中受体介导的钙振荡将导致分泌阻滞，这是急性胰腺炎的标志。本研究对急性胰腺炎的临床治疗和管理具有重要意义。(C)2013 Elsevier Inc. All rights reserved.
Although overwhelming evidence indicates that neutrophil infiltration is an early event in acute pancreatitis, the effect of neutrophil respiratory burst on pancreatic acini has not been investigated. In the present work, effect of fMLP-induced neutrophil respiratory burst on pancreatic acini was examined. It was found that neutrophil respiratory burst blocked calcium oscillations induced by cholecystokinin or by acetylcholine. Such lasting inhibition was dependent on the density of bursting neutrophils and could be overcome by increased agonist concentration. Inhibition of cholecystokinin stimulation was also observed in AR4-2J cells. In sharp contrast, neutrophil respiratory burst had no effect on calcium oscillations induced by phenylephrine (PE), vasopressin, or by ATP in rat hepatocytes. These data together suggest that inhibition of receptor-mediated calcium oscillations in pancreatic acini by neutrophil respiratory burst would lead to secretory blockade, which is a hallmark of acute pancreatitis. The present work has important implications for clinical treatment and management of acute pancreatitis. (C) 2013 Elsevier Inc. All rights reserved.