Neutrophil depletion reduces interstitial cajal-like cell injury and alleviates inflammation-induced motor dysfunction in guinea-pig gallbladder during acute cholecystitis

Objective(s): Gallbladder interstitial Cajal-like cells (ICLCs) are known as some of the players in the complex motility mechanisms affecting gallbladder motility. This study aims to explore the mechanism of guinea-pig gallbladder motility disorders during Acute Cholecystitis (AC), focusing on the relationships between neutrophil alterations, gallbladder ICLCs, and smooth muscle contractility.Materials and Methods: Forty-eight guinea pigs were randomly divided into four groups: normal, sham, common bile duct ligation (CBDL), and anti-PMN (anti-polymorphonuclear antibody treated +CBDL). Hematoxylin and eosin-stained slides from each gallbladder sample were examined for inflammation, and myeloperoxidase (MPO) activity was evaluated. The contractile response of gallbladder muscle to Ach, CCK-۸, and KCl was registered by a tension transducer, and ultrastructure features of ICLCs were observed.Results: Pretreatment with anti-PMN significantly reduced the circulating neutrophils by ۸۰% and also considerably decreased the gallbladder MPO activity by ۵۲.۹% compared with the CBDL group (P<۰.۰۵). After adding Ach, CCK-۸, and KCl, the contraction ability in CBDL and anti-PMN groups was lower than those of normal and sham groups (P<۰.۰۵), and they were increased substantially in the anti-PMN group compared with the CBDL group (P<۰.۰۵). Transmission electron microscopy confirmed that the cytoplasm of the neutrophils was full of granules, and neutrophils contacted closely with ICLCs. The ultrastructure of ICLCs in the anti-PMN group was less inflamed and the endoplasmic reticulum was mildly dilated, and cell processes also increased.Conclusion: Anti-PMN could relieve the ultrastructure injury of ICLCs and alleviate gallbladder dysmotility during AC. Neutrophils may damage gallbladder ICLCs at first followed by dysmotility.

کلیدواژه ها:

Common bile duct ligation ، Gallbladder dysmotility ، Guinea pigs ، Interstitial cajal-like cells ، Neutrophils ، Ultrastructure features