Roles of IgE and Histamine in Mast Cell Maturation

Mast cells are activated upon immunoglobulin E (IgE)-mediated antigen stimulation, and release a wide variety of mediators, including histamine to trigger inflammatory responses. The surface expression levels of Fcε receptor I (FcεRI), a high affinity receptor of IgE, were found to be positively regulated by IgE. IgE could protect murine cultured mast cells from apoptotic cell death induced by the deprivation of interleukin-3 and a certain kind of IgE could activate immature mast cells in the absence of antigens, leading to the release of pro-inflammatory cytokines and a transient increase in histamine synthesis. Histamine synthesis in mast cells was found to be required for the maturation of murine connective tissue-type mast cells, raising the possibility that IgE indirectly modulates local mast cell maturation. Although it remains controversial to what extent this concept of “monomeric IgE effects” could have relevance in the modulation of human mast cell functions, the therapeutic effects of anti-IgE antibodies might be accounted for in terms of the decreased serum IgE concentrations. Because drastic increases in serum IgE concentrations are often observed in patients with atopic dermatitis and chronic urticaria, a close investigation of the roles of IgE in mast cell maturation should contribute to development of novel therapeutic approaches for these inflammatory diseases.

Inhibitory effects of catechin isolated from Acacia catechu on ovalbumin induced allergic asthma model

Purpose Polyphenols possess anti-allergic activities. Catechin is one of the polyphenols that are abundantly present in the Acacia catechu. In this study, the authors investigated the effect of catechin isolated from A. catechu in an experimental mouse model of ovalbumin (OVA)-induced allergic asthma. Design/methodology/approach Catechin was isolated from A. catechu, and phytochemical analysis was carried out by ultraviolet visible and thin-layer chromatography (TLC), high pressure thin-layer chromatography was used for the determination of an amount of catechin present. In a first set of an experiment, the authors have carried out dose-dependent evaluation of catechin on histamine synthesis in normal rats. In another study, allergic asthma was induced in BALB/c mice by intraperitoneal injection of 50 mg OVA dissolved in 4 mg aluminum hydroxide dissolved in 0.2 ml saline on Days 0 and 14. Catechin was given orally at the dose of 100 mg/kg, once a day from Day 1 to Day 35 and after which various respiratory parameters such as tidal volume, respiratory rate and airflow rate, biochemical parameters such as histamine release from mast cells, bronchoalveolar (BAL) lavage fluid analysis and histopathology of lungs were carried out. Findings Catechin showed significant (p < 0.05) improvement in respiratory parameters such as tidal volume, respiratory rate and airflow rate, as well as biochemical and hematological parameters such as blood histamine, serum bicarbonate and nitric oxide levels as compared to the disease control group. The treatment also showed inhibitory effects on histamine synthesis in rat peritoneal as well as BAL mast cells. Also, a significant (p < 0.05) improvement in lung histopathology was observed with catechin. Originality/value From the present study, the authors can conclude that catechin exhibited potent anti-allergic activity by inhibition of histamine synthesis by inhibition of histidine decarboxylase enzyme. The study suggests that catechin has therapeutic potential for the treatment of allergic inflammatory disease in humans.

Suppression of IFN-γ Production in Murine Splenocytes by Histamine Receptor Antagonists

Accumulating evidence suggests that histamine synthesis induced in several types of tumor tissues modulates tumor immunity. We found that a transient histamine synthesis was induced in CD11b+Gr-1+ splenocytes derived from BALB/c mice transplanted with a syngeneic colon carcinoma, CT-26, when they were co-cultured with CT-26 cells. Significant levels of IFN-γ were produced under this co-culture condition. We explored the modulatory roles of histamine on IFN-γ production and found that several histamine receptor antagonists, such as pyrilamine, diphenhydramine, JNJ7777120, and thioperamide, could significantly suppress IFN-γ production. However, suppression of IFN-γ production by these antagonists was also found when splenocytes were derived from the Hdc−/− BALB/c mice. Suppressive effects of these antagonists were found on IFN-γ production induced by concanavalin A or the combination of an anti-CD3 antibody and an anti-CD28 antibody in a histamine-independent manner. Murine splenocytes were found to express H1 and H2 receptors, but not H3 and H4 receptors. IFN-γ production in the Hh1r−/− splenocytes induced by the combination of an anti-CD3 antibody and an anti-CD28 antibody was significantly suppressed by these antagonists. These findings suggest that pyrilamine, diphenhydramine, JNJ7777120, and thioperamide can suppress IFN-γ production in activated splenocytes in a histamine-independent manner.

Suppression of IFN-g Production in Murine Splenocytes by Histamine Receptor Antagonists

Accumulating evidence suggests that histamine synthesis induced in several types of tumor tissues should modulate tumor immunity. We found that a transient histamine synthesis was induced in CD11b+Gr-1+splenocytes derived from BALB/c mice transplanted with a syngeneic colon carcinoma, CT-26, when they were co-cultured with CT-26 cells. Significant levels of IFN-&gamma; were produced under this co-culture condition. We explored the modulatory roles of histamine on IFN-&gamma; production and found that several histamine receptor antagonists, such as pyrilamine, diphenhydramine, JNJ7777120, and thioperamide, could significantly suppress IFN-&gamma; production. However, suppression of IFN-&gamma; production by these antagonists was also found when splenocytes were derived from the Hdc-/- BALB/c mice. Suppressive effects of these antagonists were found on IFN-&gamma; production induced by concanavalin A or the combination of an anti-CD3 antibody and an anti-CD28 antibody in a histamine-independent manner. Murine splenocytes were found to express H1 and H2 receptors, but not H3 and H4 receptors. IFN-&gamma; production in the Hh1r-/- splenocytes induced by the combination of an anti-CD3 antibody and an anti-CD28 antibody was significantly suppressed by these antagonists. These findings suggest that pyrilamine, diphenhydramine, JNJ7777120, and thioperamide could suppress IFN-&gamma; production in activated splenocytes in histamine-independent manner.