Murine model of food allergy after epicutaneous sensitization: Role of mucosal mast cell protease-1 (1)
Two main types of mast cells have been described; tryptase-releasing connective tissue mast cells (CTMCs), and the tryptase and chymase- releasing mucosal mast cells (MMCs). Mucosal mast cell protease-1 (MMCP-1) is one of the 13 currently recognized mast cell-derived proteases in the mouse. MMCP-1 has been shown to be a tight junction-breaking protease, thus altering the permeability of the small intestine.
On day 1 and day 4, ovalbumin (OVA) or saline was placed on a patch of sterile gauze (1 x 1 cm) which was taped to the skin of the mouse’s back. On day 8 the tape was removed. On day 18 and on day 22, an identical patch was reapplied to the same skin site and removed on day 25.
After sensitizations on day 35, there was an increase in average levels of ovalbumin-specific serum IgE and IgG1 in OVA sensitized mice. When the sal-ova group was compared with the ova-ova group, there was a significant difference in both IgE and IgG1 on day 51. There was no statistical difference in ovalbumin-specific IgG2a levels between the study groups on day 35 or day 51.
There was no detectable MMCP-1 on day 0 and day 35 serum samples of the ovalbumin or sham-sensitized mice. In ova-ova group, on day 40, 18 min after the first intragastric dose, serum MMCP-1 levels increased to 1217 +/- 241 ng/ml and repeated intragastric challenges (6 times 50 mg ovalbumin) led to a massive increase in serum MMCP-1 concentration, on average 21,031 +/- 18,190 ng/ml,
TGF-b1, IL12/p35, IL-12/p40, IFN-g, CXCL-9, and CXCL-10 showed lower expression levels in the jejunum than in the ileum, independently of the sensitization group.
Dermal sensitization routes can lead to apparent systemic allergy, denoted by vigorous IgE synthesis and Th-2 dominance in the affected skin, which can be directed by appropriate challenges to target organs elsewhere in the body. Serum MMCP-1, apart from being a marker of mucosal mastocytosis and of increased gut permeability, could be a new systemic serum marker of intestinal mast cell activation also in murine food allergy models. In the production of MMCP-1 from bone marrow mast cell cultures, TGF-b1 is needed together with stem cell factor, as well as IL-3, and IL-9.