Activated Mast Cells Infiltrate in Close Proximity to Enteric Nerves in Diarrhea-predominant Irritable Bowel Syndrome

Abstract

Mast cells (MC) may be one factor influencing the response of visceral afferent nerves to mechanical and chemical stimuli. The aim of this study was to evaluate the degree of infiltration and activity of colonic MC in irritable bowel syndrome (IBS). Biopsy specimens were obtained from the cecum and rectum of 14 diarrhea predominant IBS and 14 normal controls. Electron microscopy was used to determine the number of intact and degranulated colonic MC and to quantify these separately according to the distance between MC and enteric nerves. An increased number of MC in both cecum and rectum in the IBS group in comparison with the control group was demonstrated (p<0.05). Activated MC in close proximity to enteric nerves were significantly increased in both cecum and rectum of the IBS group compared to control group (p<0.005). In addition, activated MC were significantly increased in close proximity to the nerves compared to those in the remote area in both cecum and rectum of the IBS group (p<0.0001). MC were significantly increased and activated in both cecum and rectum of the IBS group compared to controls. MC may play a role in the gut sensory hypersensitivity of IBS.

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

“…and rectum. 48,64,68,[78][79][80] These results are particularly robust for the caecum (100% of studies, 6/6) and the colon (80% of studies, 8/10), where mast cell densities can be anywhere from 50% to more than 100% higher than in healthy control patients. When available, individual data from caecum and colon samples indicate that the proportion of abnormal values (values that would be considered as outliers in healthy control datasets) in IBS patients is high, which suggests that overlap with normal tissue is limited.…”

“…Two studies have reported a correlation between mast cell density and increased intestinal permeability in IBS patients. 39,71 Finally, several studies have correlated mast cell number with the severity of abdominal pain symptoms, 64,68,73,116 especially when mast cells were found close to enteric nerves. 68,73 Further investigation is required to determine the activation state of mast cells (e.g.…”

Treatment of Diarrhea-Predominant Irritable Bowel Syndrome With Mesalazine and/or Saccharomyces Boulardii

“…These findings, associated with increased mast cell degranulation, increased spontaneous release of MC tryptase and histamine 1 and increased proximity of MC to enteric nerves in IBS, suggest a role for MC in the disturbed, sensorimotor function characteristic of this condition (3,16,26,39,40,41,58) . The proximity of MC to enteric nerves suggests that MC mediators have increased potential to activate enteric neurons (39) .…”

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

“…In patients with irritable bowel syndrome (IBS) the number of mucosal mast cells (MMC) in terminal ileum and caecum is increased [51,52]. The degranulation rate of MMC in close proximity to nerves was reported to be significantly higher than degranulation of MMC distant from nerve fibers in the colorectal specimens of diarrhea predominant IBS patients [53]. Moreover, a positive correlation was found between the severity of abdominal pain and the proximity of MMC and nerve fibers in IBS patients [35].…”