Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Dec;20(12):2364-78.
doi: 10.1097/MIB.0000000000000142.

The Multifaceted Mast Cell in Inflammatory Bowel Disease

Affiliations
Free PMC article
Review

The Multifaceted Mast Cell in Inflammatory Bowel Disease

Matthew J Hamilton et al. Inflamm Bowel Dis. .
Free PMC article

Abstract

Mast cells (MCs) are tissue-resident immune cells that carry out protective roles against pathogens. In disease states, such as inflammatory bowel disease, these granulocytes release a diverse array of mediators that contribute to inflammatory processes. They also participate in wound repair and tissue remodeling. In this review, the composition of MCs and how their phenotypes can be altered during inflammation of the gastrointestinal tract is detailed. Animal and human clinical studies that have implicated the participation of MCs in inflammatory bowel disease are reviewed, including the contribution of the cell's mediators to clinical symptoms, stress-triggered inflammation, and fistula and strictures. Studies that have focused on negating the proinflammatory roles of MCs and their mediators in animal models suggest new targets for therapies for patients with inflammatory bowel disease.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Mediators released from activated MCs. MCs express receptors that recognize different growth factors, immunoglobulins, bacterial components, and complement-derived factors. On a weight basis, ~50% of the protein content of a mature MC in the GI tract consists of varied proteases stored in the cell’s secretory granules ionically bound to serglycin proteoglycans. When MCs are activated (e.g., by their IgG receptors FcγRI and FcγRIII), they exocytose the preformed mediators from their secretory granules. Minutes to hours later, the activated MCs generate and release varied lipid mediators and cytokine/chemokine mediators, respectively. MCs are heterogeneous immune cells in tissues, and the combinations of mediators they produce are dependent on the cell’s phenotype and the activating signaling pathway.
FIGURE 2
FIGURE 2
MCs in the colonic mucosa of a patient with IBD. A patient with active UC underwent colonoscopy to determine the extent and severity of the colitis. H&E histochemistry, performed on sections of a biopsy from an inflamed segment, revealed acute and chronic inflammatory changes in the mucosa at low ×20 (A) and higher ×40 power (B). To visualize the Kit+ MCs in the biopsy, replicate sections were stained with an antibody that recognizes this tyrosine kinase receptor. Kit+ MCs were interspersed throughout the lamina propria (black arrows) at low ×20 (C) and higher ×40 power (D). There were no aggregates or sheets of MCs that would be consistent with systemic mastocytosis. Images courtesy of Jason Hornick, MD, Department of Pathology, Brigham and Women’s Hospital.
FIGURE 3
FIGURE 3
Ultrastructure of intestinal MCs in proximity to nerve endings in GI disorders. MCs are granulocytes that can be identified in tissue section by electron microscopy based on their characteristic monolobed nucleus, elongated surface folds (microplicae), and abundant cytoplasmic electron-dense granules (A). In the intestine, MCs (M) frequently reside in close proximity to blood vessels and nerves (N). Depicted are MCs adjacent to nerve endings and in various stages of activation (B–D) in a patient with IBS. White arrowheads highlight granules that are partially or completely empty. Reprinted from Giovanni Barbara et al, Gastroenterology 2007;132:p 30 with permission from Elsevier.
FIGURE 4
FIGURE 4
MCs have diverse functions in the intestine in both health and disease. MCs are tissue-resident immune cells that provide protection from invading organisms. However, they can be inappropriately activated in IBD, resulting in the release of mediators that contribute to the pathology of the GI tract. Depicted is a breach of the epithelium barrier, which results in the activation of a mucosal MC by bacterial products that make their way into the mucosa. The diverse arsenal of mediators produced and released by the activated MC leads to the accumulation of neutrophils and other inflammatory cells, further disruption of the epithelial barrier, increased ion/water transport, activation of the enteric nervous system, and ultimately wound repair and tissue remodeling.
FIGURE 5
FIGURE 5
Colonoscopy of an untreated wild-type B6 mouse (A), a DSS-treated wild-type B6 mouse (B), and a DSS-treated MC tryptase knock-out (mMCP-6–null) B6 mouse (C). The mucosal surface of the untreated wild-type B6 mouse is smooth, and its underlining blood vessels can be readily seen (green arrow). In contrast, the blood vessels of the wild-type B6 mouse that received DSS for 5 days were less visible due to the submucosal edema (blue arrow). Ulcers and erosions also were present in this DSS-treated animal. The mucosal surface of the DSS-treated mMCP-6–null B6 mouse was similar to that of the untreated wild-type mouse (green arrow). The brown matter in the center of each colon is feces.

Similar articles

See all similar articles

Cited by 14 articles

See all "Cited by" articles

Publication types

Feedback