Search

The objective of this study was to investigate the neuroimmune mechanisms implicated in the enhancement of gastrointestinal function through the administration of oral DHA. Mast cell-deficient mice (Kit W-sh ) and C57BL/6 mice were used to establish postoperative ileus (POI) models. To further validate our findings, we conducted noncontact coculture experiments involving dorsal root ganglion (DRG) cells, bone marrow-derived mast cells (BMMCs) and T84 cells. Furthermore, the results obtained from investigations conducted on animals and cells were subsequently validated through clinical trials. The administration of oral DHA had ameliorative effects on intestinal barrier injury and postoperative ileus. In a mechanistic manner, the anti-inflammatory effect of DHA was achieved through the activation of transient receptor potential ankyrin 1 (TRPA1) on DRG cells, resulting in the stabilization of mast cells and increasing interleukin 10 (IL-10) secretion in mast cells. Furthermore, the activation of the pro-repair WNT1-inducible signaling protein 1 (WISP-1) signaling pathways by mast cell-derived IL-10 resulted in an enhancement of the intestinal barrier integrity. The current study demonstrated that the neuroimmune interaction between mast cells and nerves played a crucial role in the process of oral DHA improving the intestinal barrier integrity of POI, which further triggered the activation of CREB/WISP-1 signaling in intestinal mucosal cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The persistent phase of postoperative ileus (POI) is mediated by inflammatory activation of the resident myeloid immune cell population in the gut wall, likely elicited by neurogenic activation. Mast cells are thought to play a critical role in this inflammatory response and involvement of mast cells in POI has been investigated and described thoroughly in experimental studies. Intestinal manipulation (IM) leads to degranulation of mast cells, resulting in an increase in mast cell proteases in peritoneal fluid and gut tissue. The inflammatory infiltrate formed in the intestinal wall thereby impairs gastrointestinal motility. In the clinical study by Berdun et al., the experimentally known association between mast cell degranulation and delayed motility is shown in a clinical setting. These findings are important and open up therapeutic opportunities to reduce or prevent POI. In this mini-review, the role of mast cells in POI is discussed. Furthermore, an update is given on the involvement of the inflammatory response in POI and potential therapeutic strategies., (© 2015 John Wiley & Sons Ltd.)

Background: Degranulation of peritoneal mast cells (MCs) induced by intestinal manipulation has been proposed as a pathophysiological factor in postoperative ileus (POI). We aimed to explore the relationship between peritoneal and colonic MC degranulation and gastrointestinal (GI) recovery following colectomy., Methods: Patients undergoing elective laparoscopic cholecystectomy (using a laparoscope and small abdominal incisions, n = 14), and elective laparoscopic (n = 32) or open partial colectomy (through a large abdominal incision, n = 10) were studied. MC protease tryptase and chymase were studied in peritoneal fluid at the beginning, middle, and end of each surgical intervention. Density of MCs in colectomy samples were examined and oro-caecal transit time by breath test, GI function recovery by clinical composite endpoint GI-2 and association between MC proteases and clinical recovery., Key Results: Open and laparoscopic colectomy caused greater peritoneal release of tryptase and chymase (323.0 ng/mL [IQR: 53.05-381.4] and 118.6 ng/mL [IQR: 53.60-240.3]), than cholecystectomy (41.64 ng/mL [IQR: 11.17-90.93]) at the end of the surgical intervention. However, there were no differences between laparoscopic and open colectomy. Increased peritoneal protease release during surgery was observed in patients who developed POI after colectomy., Conclusions & Inferences: Colorectal surgery causes protease release from peritoneal MCs. Protease release does not differ between both types of colectomy (laparoscopy vs laparotomy). However, MC activation is increased in colectomy patients developing POI. Therefore, degranulation of peritoneal MCs as a factor contributing to human POI after colectomy might be considered in future studies as a target to avoid POI., (© 2015 John Wiley & Sons Ltd.)

Mast cells may be regarded as prototypes of innate immune cells that can be controlled by neuronal mediators. Their activation has been implicated in many types of neuro-inflammatory responses, and related disturbances of gut motility, via direct or indirect mechanisms that involve several mechanisms relevant to disease pathogenesis such as changes in epithelial barrier function or activation of adaptive or innate immune responses. Here we review the evidence for the involvement of mast cells in the inflammation of the bowel wall caused by bowel manipulation that leads to motility disturbances such as postoperative gastroparesis and ileus. Also in IBD there is substantial evidence for the involvement of mast cells and a mast cell-mediated neuroimmune interaction showing an increased number and an increased degranulation of mast cells. We discuss the potential of mast cell inhibition as a bona fide drug target to relief postoperative ileus. Further research on mast cell-related therapy either by stabilizing the mast cells or by blocking specific mast cell mediators as adjunctive therapy in IBD is encouraged, bearing in mind that several drugs currently used in the treatment of IBD possess properties affecting mast cell activities. This article is part of a Special Issue entitled: Mast cells in inflammation., (Copyright © 2011. Published by Elsevier B.V.)

Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from decreased mast cell activation and impaired intestinal inflammation., Objective: To quantify mast cell activation and inflammation in patients undergoing conventional and minimal invasive surgery., Methods: (1) Mast cell activation (ie, tryptase release) and pro-inflammatory mediator release were determined in peritoneal lavage fluid obtained at consecutive time points during open, laparoscopic and transvaginal gynaecological surgery. (2) Lymphocyte function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) mRNA as well as leucocyte influx were quantified in non-handled and handled jejunal muscle specimens collected during biliary reconstructive surgery. (3) Intestinal leucocyte influx was assessed by 99mTc-labelled leucocyte single photon emission computed tomography (SPECT) - computed tomography (CT) scanning before and after abdominal or vaginal hysterectomy., Results: (1) Intestinal handling during abdominal hysterectomy resulted in an immediate release of tryptase followed by enhanced interleukin 6 (IL6) and IL8 levels. None of the mediators increased during minimal invasive surgery except for a slight increase in IL8 during laparoscopic surgery. (2) Jejunal ICAM-1 and iNOS mRNA transcription as well as leucocyte recruitment were increased after intestinal handling. (3) Leucocyte scanning 24 h after surgery revealed increased intestinal activity after abdominal but not after vaginal hysterectomy., Conclusions: This study demonstrates that intestinal handling triggers mast cell activation and inflammation associated with prolonged postoperative ileus. These results may partly explain the faster recovery after minimal invasive surgery and encourage future clinical trials targeting mast cells to shorten postoperative ileus.

Background & Aims: Inflammation of the intestinal muscularis following manipulation during surgery plays a crucial role in the pathogenesis of postoperative ileus. Here, we evaluate the role of mast cell activation in the recruitment of infiltrates in a murine model., Methods: Twenty-four hours after control laparotomy or intestinal manipulation, gastric emptying was determined. Mast cell degranulation was determined by measurement of mast cell protease-I in peritoneal fluid. Intestinal inflammation was assessed by determination of tissue myeloperoxidase activity and histochemical staining., Results: Intestinal manipulation elicited a significant increase in mast cell protease-I levels in peritoneal fluid and resulted in recruitment of inflammatory infiltrates to the intestinal muscularis. This infiltrate was associated with a delay in gastric emptying 24 hours after surgery. Pretreatment with mast cell stabilizers ketotifen (1 mg/kg, p.o.) or doxantrazole (5 mg/kg, i.p.) prevented both manipulation-induced inflammation and gastroparesis. Reciprocally, in vivo exposure of an ileal loop to the mast cell secretagogue compound 48/80 (0.2 mg/mL for 1 minute) induced muscular inflammation and delayed gastric emptying. The manipulation-induced inflammation was dependent on the presence of mast cells because intestinal manipulation in mast cell-deficient Kit/Kitv mice did not elicit significant leukocyte recruitment. Reconstitution of Kit/Kitv mice with cultured bone marrow-derived mast cells from congenic wild types restored the manipulation-induced inflammation., Conclusions: Our results show that degranulation of connective tissue mast cells is a key event for the establishment of the intestinal infiltrate that mediates postoperative ileus following abdominal surgery.