Basophils and mast cells are crucial for reactions due to epicutaneous sensitization to ovalbumin

Abstract

The prevalence of food allergies worldwide has increased recently. Epicutaneous sensitization to antigen could be a method to study food allergy. To clarify the mechanisms of food allergy, we established a mouse model of epicutaneous sensitization using ovalbumin (OVA). BALB/c mice were sensitized by three-time application of OVA to tape-stripped skin (1-week sensitization at 2-week intervals) and oral challenge of OVA undertaken. Rectal temperature was monitored. Blood and tissue (skin and jejunum) of challenged mice were taken. Numbers of mast cells (MCs) and basophils were counted. Serum and/or tissue levels of OVA -specific IgE and IgG antibodies and several cytokines were measured using enzyme-linked immunoassay kits. MC and basophil depletion experiments were undertaken. In OVA/epicutaneous-sensitized and orally challenged mice, systemic anaphylaxis (as evidenced by reduced rectal temperature) was observed. Levels of OVA-specific IgE and IgG antibodies were increased in these mice, as were increased number of MCs and basophils. Serum levels of MC protease 1 were increased significantly. Basophil and MC depletion experiments revealed that they both participate in reactions. Increased production of thymic stromal lymphopoietin (TSLP) at skin sites of OVA sensitization was noted. We speculate that TSLP produced from epidermal cells during antigen sensitization can enable basophils to promote a T helper (Th)2 immune reaction, leading to and systemic anaphylaxis by antigen-specific IgE-bearing MCs. This TSLP-basophils-MC axis could be a novel therapeutic target against food allergy.

Ingestion of Casein Hydrolysate Induces Oral Tolerance and Suppresses Subsequent Epicutaneous Sensitization and Development of Anaphylaxis Reaction to Casein in Mice

“…Two independent groups [22, 28] reported that the number of mast cells in the small intestine increased after oral antigen challenge in tape-stripping epicutaneously sensitized mice. By contrast, another group [30] reported an increased number of basophils, but not mast cells, in the jejunum after oral OVA challenge in OVA-epicutaneously sensitized mice. Such discrepancy in the behavior of intestinal immune cells might be related to the difference in experimental designs among studies, such as the frequency of sensitizations and the timing of histological observation.…”

“…Several studies have demonstrated that the accumulation of immune cells in intestine was observed in epicutaneously sensitized mouse models [22, 28-30]. To determine whether immune cells accumulation could be observed in our model, histological analysis was performed.…”

“…Previous studies also indicated that the extent of rectal temperature drop in an anaphylactic reaction is influenced by the number [28] and dosage [30] of the challenge agent.…”

“…Furthermore, an increase of basophils was observed in the small intestine of epicutaneously sensitized mice, which was also suppressed by oral tolerance induction. Basophils are known to play an important role in the anaphylaxis reaction as effector cells in epicutaneously sensitized mice [30]. Thus, the suppression of basophilic accumulation in the small intestine of casein- and CNH-fed mice might have contributed to the observed alleviation of their anaphylaxis reaction.…”

Organization of the Skin Immune System and Compartmentalized Immune Responses in Infectious Diseases

“…According to their tissue distribution and enzymatic composition of their granules, it is possible to distinguish at least two subpopulations of mast cells: mucosal mast cells, which contain trypsin, and connective tissue mast cells, which contain chymotrypsin. A high-affinity receptor for IgE is expressed by basophils and mast cells, which is strongly bound to their surfaces, leading to degranulation and the release of various substances, including serotonin, histamine, platelet-activating factor, and leukotrienes (Table 1) (133,134).…”