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

Abstract

Kraneveld, Aletta D., Thea Muis, Andries S. Koster, and Frans P. Nijkamp. Role of mucosal mast cells in early vascular permeability changes of intestinal DTH reaction in the rat. Am. J. Physiol. 274 (Gastrointest. Liver Physiol. 37): G832-G839, 1998.-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. small intestinal vascular permeability; capsaicin CONSIDERABLE EVIDENCE supports a role for mast cells in immunologic inflammatory processes (6). Also, in cellmediated delayed-type hypersensitivity (DTH) reactions a role for mast cells has been postulated (9, 25). DTH reactions in the gastrointestinal tract have been proposed to represent some of the features prevalent in inflammatory bowel diseases (IBD); ongoing responses have been associated with an increased vascular permeability and enhanced lymphocyte infiltration into the inflamed intestinal tissue (10,13,31). Most of the studies investigating the role of mast cells in DTH reactions have been done in the intestine, lung, and skin of Trichinella spiralis-infected mice and picryl chloride contact-sensitized mice (9,(25)(26)(27). It has been suggested that on contact sensitization with picryl chloride or after primary helminth infection, DTHinitiating cells in lymphoid organs are induced to release antigen-specific factors that bind systemically to mast cells (4,15,22,36). On local challenge with the antigen, the armed mast cells are activated to release serotonin. Activation of serotonin receptor on vascular endothelium induces a local increase in vascular...

Critical Role for Mast Cells in the Pathogenesis of 2,4-Dinitrobenzene-Induced Murine Colonic Hypersensitivity Reaction

“…This DTH-like reaction is classically known as a non-IgE-mediated reaction. Induction of DTH reactions with DNFB has been shown to lead to successful models for contact dermatitis, nonatopic asthma, and small intestinal inflammation (18,29,30). An acute response occurs within 6 h after challenge and is a result of direct mast cell activation and degranulation.…”

“…4. Also the number of CAE-positive mast cells was increased after DNFB sensitization and DNS challenge compared with vehiclesensitized and DNS-challenged mice (mast cell number per colon: vehicle/DNS 16 (6 -22), DNFB/DNS 28 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36); results are expressed as median (range); p Ͻ 0.05, n ϭ 6). TNF-␣ is one of the major cytokines released upon mast cell activation.…”

Murine Model for Non-IgE-Mediated Asthma

“…The lymphocyte and the mast cell are two key inflammatory cells in the non-atopic reactions in the mouse airways as well as the skin and the intestine (7,30,31). In skin studies, it has been demonstrated that, upon contact sensitization, B lymphocytes are activated to produce hapten-specific immunoglobulin kappa light chains (IgLC) in spleen and lymph nodes (32).…”

Role of Chymase-Dependent Angiotensin II Formation in Regulating Blood Pressure in Spontaneously Hypertensive Rats

“…RMCP I may be involved in cardiovascular remodeling via the degradation of fibronectin (22,23) and by the activation of transforming growth factor-β (24,25). On the other hand, RMCP II may contribute to an increase of vascular permeability (26). Therefore, the upregulated chymases, RMCP I and RMCP II, that are found in SHR vascular tissues may be involved in remodeling vascular structures rather than in regulating blood pressure.…”