Effect of Neutrophils on Gallbladder Interstitial Cajal-Like Cells in Guinea Pig Model of Acute Cholecystitis

Huang, Zhenpeng; Qiu, Hu; Yang, Yan; Yu, Baoping

doi:10.1159/000447899

Cited by 8 publications

(11 citation statements)

References 30 publications

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“…In AC, biliary tract obstruction leads to ICC injury in the gallbladder. This then blocks c-kit receptors, and results in gallbladder ICC loss, increased ICC apoptosis, and a lack of regeneration and maintenance of ICC networks [32,33]. c-kit receptors modulate the generation and rhythmicity of electrical activity to regulate the excitability of gallbladder smooth muscle cells [27].…”

Section: Discussionmentioning

confidence: 99%

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis

Huang¹,

Qiu²,

Yu³

2018

Cell Physiol Biochem

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Background/Aims: Acute cholecystitis is a common gastrointestinal disorder, often characterized by acute cholecystitis with gallbladder motility disorder. Interstitial cells of Cajal (ICCs) are the pacemaker cells of gut motility in the gastrointestinal tract. Disruption of ICC function is related to motility disorders. The aim of this study was to explore the cellular and molecular mechanisms of ICCs in acute cholecystitis and after the resolution of acute inflammation. Materials and Methods: Fifty adult guinea pigs were randomly divided into five groups: a sham-administered group (control group); two groups that were intraperitoneally administered an anti-polyclonal neutrophil (PMN) antibody 24 h before common bile duct ligation (CBDL); and two groups of guinea pigs that were subjected to CBDL without receiving the PMN antibody. Guinea pigs that underwent CBDL were held for 24 h or 48 h after surgery before being subjected to laparotomy and cholecystectomy. Immunohistochemistry, TUNEL assays, western blotting, and real-time PCR were performed to determine ICC morphology and density, to detect ICC apoptosis, and to examine stem cell factor (SCF) and c-kit protein expression and SCF and c-kit mRNA levels, respectively. Results: Both hematoxylin-eosin staining and histological inflammation scores in the PMN groups were lower than those in the control groups (P < 0.01). No differences were observed in ICC morphology between groups. During acute cholecystitis, ICCs numbers were reduced. Conversely, the density of ICCs increased after inflammation was relieved (P < 0.01). In addition, SCF and c-kit protein and mRNA expression levels decreased during acute cholecystitis (P < 0.05) and increased after inflammation was relieved (P < 0.05). Furthermore, ICC apoptosis increased during acute cholecystitis and decreased after resolution of acute cholecystitis (P < 0.01). Conclusions: In acute cholecystitis, ICC injury may be related to gallbladder motility disorder.

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Section: Discussionmentioning

confidence: 99%

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis

Huang¹,

Qiu²,

Yu³

2018

Cell Physiol Biochem

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“…Neutrophil-mediated ICLC degradation likely occurs via phagocytosis and destruction of enzymes, such as myeloperoxidase, lysozyme, and alkaline phosphatase. In addition to this direct impact on ICLCs, neutrophils cause indirect damage through the downregulation of SCF, c-kit (Huang, Qiu, Yang, Yu, 2016), and other key signaling molecules, such as neuronal originated nitric oxide (Choi et al, 2007), 5-HT 2 B receptor (Wouters et al, 2007) It is also important to note that neutrophils may not be the only immune cell affecting gallbladder ICLCs during acute cholecystitis.…”

Section: Discussionmentioning

confidence: 99%

“…The adult guinea pigs were randomly divided into four groups: Control group, 24 hr common bile duct ligation (CBDL) group, 48‐hr CBDL group, and antipolymorphonuclear neutrophil (PMN) group. CBDL was performed in the last three groups to induce acute cholecystitis as previously described (Huang, Qiu, Yang, Zhang, et al, ). Briefly, the common bile duct was bluntly separated and ligated with 5‐0 surgical sutures.…”

Section: Methodsmentioning

confidence: 99%

“…Neutrophils are the most cells involved in the early inflammatory response in this tissue. In fact, coculturing gallbladder ICLCs with neutrophils in vitro significantly enhanced cell apoptosis and decreased SCF and c‐kit expression (Huang, Qiu, Yang, & Yu, ). Therefore, it is possible that neutrophils play an important role in gallbladder ICLC damage–loss, as well as the subsequent gallbladder dysmotility during acute cholecystitis.…”

Section: Introductionmentioning

confidence: 99%

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Neutrophils injure gallbladder interstitial Cajal‐like cells in a guinea pig model of acute cholecystitis

Lin

Chen

Huang

et al. 2018

Journal Cellular Physiology

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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, 24 hr 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.

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“…Cholecystitis is characterized by an inflammatory process involving leukocytes infiltration of gallbladder wall 1,2 . Neutrophils and other immune cells play a deleterious role by releasing local hormones and reactive oxygen species (ROS) (for a review see 3 ), and through interactions with interstitial cells of Cajal 4 …”

Section: Introductionmentioning

confidence: 99%

Monochloramine effects on gallbladder contractility

Hernández‐Moreno

Morales

Camello-Almaraz

et al. 2020

Clin Exp Pharma Physio

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Digestive inflammatory processes induce motility alterations associated with an increase in reactive oxygen species production, including monochloramine (NH2Cl). The aim of the study was to characterize the effects of the naturally occurring oxidant monochloramine in the guinea pig gallbladder. We used standard in vitro contractility technique to record guinea pig gallbladder strips contractions. NH2Cl caused a concentration‐dependent contraction which was reduced by inhibition of extracellular Ca2+ influx and tyrosine kinase pathways. The PKC antagonist GF109203X also reduced the response but not after previous tyrosine kinase inhibition, suggesting that PKC is activated by tyrosine kinase activity. The NH2Cl contractile effect was also reduced by inhibitors of mitogen‐activated protein kinase (MAPK), nitric oxide synthase, phospholipase A2 and cyclooxygenase. In addition, NH2Cl impaired the responses to CCK, tissue depolarization and electrical field stimulation. In conclusion, we present new evidence that monochloramine impairs not only the gallbladder response to CCK but also to membrane depolarization and nervous plexus stimulation, and that tyrosine kinase, PKC, MAPK and NO pathways are involved in the contractile direct effect of monochloramine.

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Effect of Neutrophils on Gallbladder Interstitial Cajal-Like Cells in Guinea Pig Model of Acute Cholecystitis

Cited by 8 publications

References 30 publications

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis

Acute Cholecystitis Reduces Interstitial Cells of Cajal in Porcine Gallbladder Through Decreased mRNA Synthesis

Neutrophils injure gallbladder interstitial Cajal‐like cells in a guinea pig model of acute cholecystitis

Monochloramine effects on gallbladder contractility

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