A rat model of intestinal hypersensitivity: mucosal mast cell activation following repeated feeding of antigen

The gastrointestinal tract harbours the largest population of mast cells in the body; this highly specialised leukocyte cell type is able to adapt its phenotype and function to the microenvironment in which it resides. Mast cells react to external and internal stimuli thanks to the variety of receptors they express, and carry out effector and regulatory tasks by means of the mediators of different natures they produce. Mast cells are fundamental elements of the intestinal barrier as they regulate epithelial function and integrity, modulate both innate and adaptive mucosal immunity, and maintain neuro-immune interactions, which are key to functioning of the gut. Disruption of the intestinal barrier is associated with increased passage of luminal antigens into the mucosa, which further facilitates mucosal mast cell activation, inflammatory responses, and altered mast cell–enteric nerve interaction. Despite intensive research showing gut dysfunction to be associated with increased intestinal permeability and mucosal mast cell activation, the specific mechanisms linking mast cell activity with altered intestinal barrier in human disease remain unclear. This review describes the role played by mast cells in control of the intestinal mucosal barrier and their contribution to digestive diseases.

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Role of mucosal mast cells in early vascular permeability changes of intestinal DTH reaction in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.274.5.g832 ◽

1998 ◽

Vol 274 (5) ◽

pp. G832-G839 ◽

Cited By ~ 3

Author(s):

Aletta D. Kraneveld ◽

Thea Muis ◽

Andries S. Koster ◽

Frans P. Nijkamp

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Activation ◽

Vascular Leakage ◽

Mast Cell Activation ◽

Mucosal Mast Cell ◽

Mucosal Mast Cells

Previously, it was shown that depletion and stabilization of the mucosal mast cell around the time of challenge were very effective in reducing delayed-type hypersensitivity (DTH) reactions in the small intestine of the rat. The role of mucosal mast cells in the early component of intestinal DTH reaction was further investigated in this study. In vivo small intestinal vascular leakage and serum levels of rat mast cell protease II (RMCP II) were determined within 1 h after intragastric challenge of rats that had been sensitized with dinitrobenzene 5 days before. A separate group of rats was used to study vasopermeability in isolated vascularly perfused small intestine after in vitro challenge. To investigate the effects of mast cell stabilization on the early events of the DTH reaction, doxantrazole was used. The influence of sensory nerves was studied by means of neonatal capsaicin-induced depletion of sensory neuropeptides. Within 1 h after challenge, a significant increase in vascular permeability was found in vivo as well as in vitro. This was associated with a DTH-specific increase in RMCP II in the serum, indicating mucosal mast cell activation. In addition, doxantrazole treatment and caspaicin pretreatment resulted in a significant inhibition of the DTH-induced vascular leakage and an increase in serum RMCP II. These findings are consistent with an important role for mucosal mast cells in early vascular leakage changes of intestinal DTH reactions. In addition, sensory nervous control of mucosal mast cell activation early after challenge is demonstrated.

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Regulation of mucosal mast cell activation by short interfering RNAs targeting syntaxin4

Immunology and Cell Biology ◽

10.1038/icb.2011.41 ◽

2011 ◽

Vol 90 (3) ◽

pp. 337-345 ◽

Cited By ~ 8

Author(s):

Shuang Liu ◽

Agung Endro Nugroho ◽

Masachika Shudou ◽

Kazutaka Maeyama

Keyword(s):

Mast Cell ◽

Cell Activation ◽

Mast Cell Activation ◽

Mucosal Mast Cell

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Experimental intestinal hyper sensitivity. Effect of four anti-allergic drugs on protein uptake, permeability to sugars and mucosal mast-cell activation

Clinical & Experimental Allergy ◽

10.1111/j.1365-2222.1995.tb01076.x ◽

1995 ◽

Vol 25 (5) ◽

pp. 448-455 ◽

Cited By ~ 5

Author(s):

M. W. TURNER ◽

P. BOULTON ◽

S. STROBEL

Keyword(s):

Mast Cell ◽

Cell Activation ◽

Mast Cell Activation ◽

Mucosal Mast Cell ◽

Protein Uptake ◽

Hyper Sensitivity

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Rno-miR-199a-3p targets Nedd4 to promote sensitization of ST36 acupoints via mast cell activation in a rat model of knee osteoarthritis

10.21203/rs.3.rs-929701/v1 ◽

2021 ◽

Author(s):

Wenchuan Qi ◽

Baitong Liu ◽

Yilu Jiang ◽

Xinye Luo ◽

Zhiwei Li ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Knee Osteoarthritis ◽

Histamine Release ◽

Rat Model ◽

Cell Activation ◽

Molecular Mechanisms ◽

Ectopic Expression ◽

The Body ◽

Mast Cell Activation

Abstract Selecting routine points on related meridians is widely accepted as the foundational principle of acupuncture. When the body is suffering disease or injury, corresponding acupoints are thought to be activated and manifest in several sensitized forms. Sensitized acupoints hold high clinical value as a reflection of disease activity on the body surface. Mast cells have been implicated in the process of acupoint sensitization but the underlying regulatory mechanisms remain unclear. In the present study, we evaluated ST36 as a sensitized acupoint in the monosodium iodoacetate-induced knee osteoarthritis rat model. We first confirmed sensitization at the ST36 acupoint through decreases in the acupoint mechanical pain threshold and instructively found an accompanying increase in skin mast cell degranulation. Thereafter, we used highthroughput RNA sequencing to reveal potential molecular mechanisms of acupoint sensitization. We showed that rno-miR-199a-3p was highly expressed in the sensitized ST36 acupoint and its expression was associated with mast cells. Functional experiments revealed that overexpression of rno-miR-199a-3p increased mast cell histamine release whereas inhibition of rno-miR-199a-3p decreased histamine release. Mechanistically, we established rno-miR-199a-3p acted to inhibit neural precursor cell expressed developmentally down-regulated 4 (Nedd4) protein expression through miRNA-mediated targeting of the 3’-UTR of Nedd4 mRNA. Moreover, we found ectopic expression of Nedd4 antagonized histamine release in mast cells and blocked the actions of rno-miR-199a-3p overexpression. Thus, our study establishes that mast cells participate in the process of acupoint sensitization, and further reveals a novel miRNA-based mechanism which is crucial for further understanding of acupoint sensitization and acupuncture applications.

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