Reduced immunostaining for c-kit receptors in mucosal mast cells in inflammatory bowel disease

J Gastroenterol Hepatol. 2007 Dec;22(12):2338-43. doi: 10.1111/j.1440-1746.2007.05011.x. Epub 2007 Jul 20.


Background and aim: The deleterious effects of stress in inflammatory bowel disease (IBD) have been attributed to activation of the brain-gut axis (BGA) and its end effectors, mast cells (MC). We previously showed that cold pressor stress test (CPT) results in increased activation and degranulation (but not increased proliferation) of mucosal MC, mitochondrial damage to epithelial cells and mucosal protein oxidation in both healthy controls and IBD patients. These changes are more marked in IBD patients. This increased activation of MC in IBD could be due to (i) greater activation of the BGA or (ii) inherited or acquired abnormalities in mucosal MC. In the current study we investigated the latter possibility.

Methods: To assess the effects of stress on mucosal MC in patients with IBD, seven controls and 15 subjects with inactive IBD underwent 5 consecutive days of CPT to activate the BGA. Endoscopic mucosal biopsies of the distal sigmoid colon were taken during unprepared sigmoidoscopy before the first CPT and after the last CPT, and formalin-fixed samples were stained for both MC granules (MCg) and for the c-kit receptor, which is present on MC membranes (MCm). Mast cell degranulation was assessed using electron microscopy.

Results: Mast cell granule staining suggested that IBD subjects do not have a significantly different number of MC compared with controls, either before or after stress. Mast cell membrane staining, in contrast, suggested that MC c-kit immunostaining was significantly reduced - at both baseline (P = 0.01) and post stress (P = 0.04) samples - in IBD patients compared to controls. MC c-kit immunostaining was independent of stress-induced MC degranulation. There was no significant change in MC number as a result of the stress intervention using either staining method in both groups.

Conclusion: These data support our previous report that the size of the mucosal MC population in patients with inactive IBD is not altered by disease or by stress, yet MC in IBD are different (fewer c-kit receptors) and respond differently (greater activation) than MC in control subjects. It remains to be seen whether this abnormality is an inherited or acquired one and to identify its role and mechanism in tissue injury in the pathogenesis of IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Count
  • Female
  • Humans
  • Immunohistochemistry
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / pathology*
  • Inflammatory Bowel Diseases / psychology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology*
  • Male
  • Mast Cells / metabolism*
  • Mast Cells / pathology*
  • Middle Aged
  • Proto-Oncogene Proteins c-kit / metabolism*


  • Proto-Oncogene Proteins c-kit