Neutrophils injure gallbladder interstitial Cajal-like cells in a guinea pig model of acute cholecystitis
Neutrophils injure gallbladder interstitial Cajal-like cells in a guinea pig model of acute cholecystitis
复制标题
中性粒细胞损伤急性胆囊炎豚鼠模型中的胆囊间质卡哈尔样细胞
DOI：
10.1002/jcp.27197
复制
发表时间：
2019-04-01
影响因子：
5.6
通讯作者：
Yu, Bao-Ping
中科院分区：
文献类型：
--
作者：
Lin, Meng-Juan;Chen, Lei;Yu, Bao-Ping
急性胆囊炎是胆囊动力障碍的常见疾病。疾病发病机制涉及免疫细胞浸润以及胆囊间质卡哈尔样细胞（ICLC）的变化。然而，目前尚不清楚免疫细胞是否或如何影响急性胆囊炎期间胆囊组织中ICLC的形态、密度、分布和功能。在这项研究中，我们在豚鼠模型中探讨了胆囊 ICLC 中与急性胆囊炎相关的改变，重点关注邻近中性粒细胞的影响。成年豚鼠被随机分为四组（对照组、24 小时胆总管结扎 [CBDL]、48 小时 CBDL 和抗多形核中性粒细胞 [PMN] 处理），并使用亚甲蓝染色和免疫荧光进行分析。还监测胆囊收缩力。为了培养胆囊 ICLC，对 10 至 15 日龄豚鼠的组织进行胶原酶消化。术后 48 小时从实验动物外周血中分离出的中性粒细胞也与胆囊 ICLC 共培养。使用 Fluo-4 AM 染料检测细胞内钙。我们的研究结果表明，急性胆囊炎期间胆囊 ICLC 密度显着下降，并伴有细胞突起缩短和网络状结构受损。然而，抗 PMN 预处理部分阻止了这些变化。急性胆囊炎期间胆囊收缩也显着减少，这似乎是由中性粒细胞介导的。此外，与中性粒细胞共培养的 ICLC 也缩短和减少了过程，并损害了网络状结构的形成。当与中性粒细胞共培养时，细胞内钙瞬变对收缩激动剂和抑制剂不太敏感。总而言之，中性粒细胞极大地影响急性胆囊炎期间的胆囊 ICLC 和运动障碍。
Acute cholecystitis is a common disease with gallbladder dysmotility. Disease pathogenesis involves immune cell infiltration as well as changes in gallbladder interstitial Cajal-like cells (ICLCs). However, it remains unclear if or how the immune cells affect ICLC morphology, density, distribution, and function in gallbladder tissue during acute cholecystitis. In this study, we explored the acute cholecystitis-related alterations in gallbladder ICLCs in a guinea pig model, focusing on the effects of neighboring neutrophils. Adult guinea pigs were randomly divided into four groups (control, 24hr common bile duct ligation [CBDL], 48-hr CBDL, and antipolymorphonuclear neutrophil [PMN] treated) and analyzed using methylene blue staining and immunofluorescence. Gallbladder contractility was also monitored. To culture gallbladder ICLCs, collagenase digestion was performed on tissue from 10- to 15-day-old guinea pigs. Neutrophils isolated from the peripheral blood of experimental animals 48-hr postsurgery were also cocultured with the gallbladder ICLCs. Intracellular calcium was detected with Fluo-4 AM dye. Our results showed that gallbladder ICLC density significantly declined during acute cholecystitis and was accompanied by shortening of the cellular processes and damage to their network-like structure. However, pretreatment with anti-PMN partially prevented these changes. Gallbladder contraction was also significantly decreased during acute cholecystitis, and this appeared to be mediated by the neutrophils. Moreover, ICLCs cocultured with neutrophils also had shortened and reduced processes and impaired network-like structure formation. Intracellular calcium transient was less sensitive to contraction agonists and inhibitors when cocultured with neutrophils. Taken together, neutrophils greatly affect gallbladder ICLCs and dysmotility during acute cholecystitis.