Calcium in Pancreatitis … Immune Cells, Too?
Calcium in Pancreatitis … Immune Cells, Too?
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DOI：
10.1093/function/zqaa030
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Liddle RA
中科院分区：
文献类型：
--
作者：
Vigna SR;Liddle RA
在本期杂志中，Gryshchenko等人描述了体外小鼠胰腺小叶中胰腺巨噬细胞（PM）的鉴定和特征。1近年来对急性胰腺炎发病机制的认识取得了很大进展。[2]体内实验动物模型的使用是这一进展的部分原因，但对急性胰腺炎基本机制的大部分认识来自各种胰腺组织制备物的体外研究。大多数体外胰腺外分泌的生理和病理生理学研究都是利用胰腺腺泡进行的。腺泡是胰腺外分泌的功能单位，主要由分泌消化酶的腺泡细胞和一些星状细胞组成。胰腺外分泌中也有许多其他类型的细胞，如导管细胞、中心腺泡细胞、结缔组织细胞、免疫细胞等，但通常不知道胰腺腺泡中含有这些细胞类型。采用胶原酶温和消化法和物理剪切法制备大鼠、豚鼠和小鼠等啮齿类动物的胰腺腺泡，揭示了正常生理中消化酶刺激-分泌偶联和胰腺炎病理生理中急性炎症反应的基本机制。胰腺外分泌功能的其他方面的一些见解也已获得使用其他体外制剂，如胰腺小叶，以证明内在的胰腺神经在蝎毒素诱导的酶分泌和急性胰腺炎的作用5;腺泡不包含神经。胰腺小叶比腺泡大，可以通过用缓冲液使胰腺膨胀，然后用剪刀简单分离或非常温和的胶原酶消化来制备。胰腺的分化及其再生也已经使用胰腺类器官的组织培养在体外进行了研究。6大多数胰腺外分泌功能的研究都是为了了解腺泡细胞在正常生理和病理（如胰腺炎）中的作用。这是因为腺泡细胞分泌消化酶，并且因为人和研究动物中急性胰腺炎的标志是腺泡细胞的损伤，导致消化酶如α-淀粉酶和脂肪酶释放到血液中，胰蛋白酶释放到胰腺细胞外空间中，水肿和坏死。分离的单个腺泡细胞在体外不能很好地存活7，这导致胰腺腺泡被广泛用于这些研究。虽然胰腺腺泡已被证明是研究早期腺泡细胞对损伤的反应的宝贵工具，但胰腺炎是一个复杂的生物学过程，涉及胰腺腺泡细胞损伤和随后的炎症反应。仅使用胰腺腺泡在体外模拟这一过程是不完整的。在这篇文章中，Gryshchenko等人鉴定并表征了胰腺小叶中的巨噬细胞。1尚不清楚是否使用小叶是因为腺泡不含巨噬细胞，或者是否未检查腺泡。通过免疫细胞化学和核形态学鉴定PMs。这些细胞在以前的出版物中被称为“X”细胞。8在这篇文章中，细胞内Ca 2+信号响应于不同的代理人的特点是在PM和比较在相邻的腺泡细胞和星状细胞的Ca 2+信号（图1）。他们表明，PM表达嘌呤能受体，鉴定为P2 Y1和P2 Y13受体，对三磷酸腺苷（ATP）和二磷酸腺苷（ADP）敏感，通过从内部储存释放Ca 2+，然后储存在细胞内。
In this issue of the Journal, Gryshchenko et al. describe the identification and characterization of pancreatic macrophages (PMs) in mouse pancreatic lobules in vitro. 1 Much progress has been made in recent years in the understanding of the mechanisms of acute pancreatitis. 2 The use of experimental animal models in vivo has accounted for some of this progress, but most of the insight into the fundamental mechanisms underlying acute pancreatitis has come from studies of various pancreatic tissue preparations in vitro. Most studies of the physiology and pathophysiology of the exocrine pancreas in vitro have been performed using pancreatic acini. The acinus is the functional unit of the exocrine pancreas and consists mainly of digestive enzyme-secreting acinar cells and some stellate cells. 3, 4 Many other cell types are also in the exocrine pancreas such as duct cells, centroacinar cells, connective tissue cells, immune cells, and others, but it is generally not known that pancreatic acini contain these cell types. Pancreatic acini prepared from rodents such as rats, guinea pigs, and mice by gentle collagenase digestion and physical shearing forces have been used to reveal the basic mechanisms of digestive enzyme stimulus-secretion coupling in normal physiology and acute inflammation in pancreatitis pathophysiology. Some insight into other aspects of exocrine pancreatic function has also been obtained using other in vitro preparations such as pancreatic lobules to demonstrate the role of intrinsic pancreatic nerves in scorpion toxin-induced enzyme secretion and acute pancreatitis 5; acini do not contain nerves. Pancreatic lobules are larger than acini and can be prepared by inflating the pancreas with buffer followed either by simple dissection with scissors or by very gentle collagenase digestion. Differentiation of the pancreas and its regeneration has also been studied using tissue culture of pancreatic organoids in vitro. 6Most studies of exocrine pancreatic function are directed at understanding the role of acinar cells in normal physiology and in pathologies such as pancreatitis. This is because acinar cells secrete digestive enzymes and because the hallmarks of acute pancreatitis in people and research animals are damage to acinar cells resulting in release of digestive enzymes such as a-amylase and lipase into the blood and trypsin into the pancreatic extracellular spaces, edema, and necrosis. Isolated, single acinar cells do not survive well in vitro 7 and this has led to the widespread use of pancreatic acini for these studies. Although pancreatic acini have proven invaluable for studying early acinar cell responses to injury, pancreatitis is a complicated biological process that involves both pancreatic acinar cell damage and a subsequent inflammatory response. Modeling this process in vitro is incomplete using only pancreatic acini. In this article, Gryshchenko et al. identify and characterize macrophages in pancreatic lobules. 1 It is not clear whether lobules were used because acini do not contain macrophages or whether acini were not examined. The PMs were identified by immunocytochemistry and by nuclear morphology. These cells had been termed “X” cells in a previous publication. 8 In this article, intracellular Ca2+ signals in response to various agents are characterized in PMs and compared with the Ca2+ signals in neighboring acinar cells and stellate cells (Figure 1). They show that PMs express purinergic receptors, identified pharmacologically as P2Y1 and P2Y13 receptors, sensitive to adenosine triphosphate (ATP) and adenosine diphosphate (ADP) that signal intracellularly via releasing Ca2+ from internal stores followed by store …
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DOI：
10.1113/jp275395
发表时间：
2018-07
期刊：
The Journal of physiology
影响因子：
--
作者：
Gryshchenko O;Gerasimenko JV;Peng S;Gerasimenko OV;Petersen OH
通讯作者：
Petersen OH
胆汁酸会诱导胰腺星状细胞坏死，依赖于钙进入和钠驱动的胆汁摄取。
DOI：
10.1113/jp272774
发表时间：
2016-11-01
期刊：
The Journal of physiology
影响因子：
--
作者：
Ferdek PE;Jakubowska MA;Gerasimenko JV;Gerasimenko OV;Petersen OH
通讯作者：
Petersen OH
影响因子：
11.4
作者：
Huch, Meritxell;Bonfanti, Paola;Boj, Sylvia F.;Sato, Toshiro;Loomans, Cindy J. M.;van de Wetering, Marc;Sojoodi, Mozhdeh;Li, Vivian S. W.;Schuijers, Jurian;Gracanin, Ana;Ringnalda, Femke;Begthel, Harry;Hamer, Karien;Mulder, Joyce;van Es, Johan H.;de Koning, Eelco;Vries, Robert G. J.;Heimberg, Harry;Clevers, Hans
通讯作者：
Clevers, Hans
DOI：
10.1113/jp271468
发表时间：
2016-01-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Gryshchenko O;Gerasimenko JV;Gerasimenko OV;Petersen OH
通讯作者：
Petersen OH
巨噬细胞表型转换协调急性胰腺炎损伤后的炎症和修复/再生
影响因子：
11.1
作者：
Wu, Jinghua;Zhang, Li;Xue, Jing
通讯作者：
Xue, Jing