Division of Allergy and Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
J Allergy Clin Immunol. 2010 Dec;126(6):1208-17.e3. doi: 10.1016/j.jaci.2010.09.013.
Mast cells and basophils are key effector cells of IgE-mediated anaphylactic reactions. The Chinese herbal formula, food allergy herbal formula 2 (FAHF-2), protects against peanut anaphylaxis in mice. However, the mechanisms underlying this effect are not fully elucidated.
To investigate whether FAHF-2 inhibits mast cell/basophil numbers and IgE-mediated activation.
Mice with peanut allergy (PNA mice) were treated with FAHF-2 intragastrically for 7 weeks and challenged intragastrically with peanut 1 day and 4 weeks posttreatment. Peripheral blood basophil numbers and peritoneal mast cell numbers and FcεRI expression were determined. Direct effects of FAHF-2 on the murine mast cell line MC/9, and effects of 4 fractions and 3 compounds isolated from FAHF-2 on rat basophilic leukemia cells (RBL-2H3) and human skin mast cells degranulation and on the IgE-mediated spleen tyrosine kinase signaling pathway, were determined.
Although all sham-treated PNA mice developed anaphylaxis, FAHF-2-treated PNA mice were protected against anaphylaxis after peanut challenge at 1 day and 4 weeks posttherapy. Reduction of peripheral blood basophils began after 1 week of treatment and continued for at least 4 weeks posttherapy. The number and FcεRI expression of peritoneal mast cells were also significantly decreased 4 weeks posttherapy. FAHF-2-treated MC/9 cells showed significantly reduced IgE-induced FcεRI expression, FcεRI γ mRNA subunit expression, proliferation, and histamine release on challenge. Fraction 2 from FAHF-2 inhibited RBL-2H3 cell and human mast cell degranulation. Three compounds from fraction 2-berberine, palmatine, and jatrorrhizine-inhibited RBL-2H3 cell degranulation via suppressing spleen tyrosine kinase phosphorylation.
Food allergy herbal formula 2 reduction of basophils and mast cell numbers as well as suppression of IgE-mediated mast cell activation may contribute to FAHF-2's persistent protection against peanut anaphylaxis.
肥大细胞和嗜碱性粒细胞是 IgE 介导的过敏反应的关键效应细胞。中草药配方食物过敏草药配方 2(FAHF-2)可保护小鼠免受花生过敏。然而,其作用机制尚未完全阐明。
研究 FAHF-2 是否抑制肥大细胞/嗜碱性粒细胞数量和 IgE 介导的激活。
用 FAHF-2 灌胃治疗花生过敏(PNA)小鼠 7 周,在治疗后 1 天和 4 周时经胃内挑战花生。检测外周血嗜碱性粒细胞数和腹腔肥大细胞数及 FcεRI 表达。测定 FAHF-2 对鼠肥大细胞系 MC/9 的直接作用,以及从 FAHF-2 中分离的 4 个馏分和 3 个化合物对大鼠嗜碱性白血病细胞(RBL-2H3)和人皮肤肥大细胞脱颗粒以及 IgE 介导的脾酪氨酸激酶信号通路的作用。
尽管所有假处理 PNA 小鼠均发生过敏反应,但在治疗后 1 天和 4 周时经胃内挑战花生后,FAHF-2 治疗的 PNA 小鼠均受到保护,免受过敏反应。治疗后 1 周开始减少外周血嗜碱性粒细胞,并持续至少 4 周。治疗后 4 周,腹腔肥大细胞的数量和 FcεRI 表达也明显减少。FAHF-2 处理的 MC/9 细胞在 IgE 诱导的 FcεRI 表达、FcεRIγmRNA 亚基表达、增殖和组胺释放方面显示出明显减少。FAHF-2 的馏分 2 抑制 RBL-2H3 细胞和人肥大细胞脱颗粒。馏分 2 中的 3 种化合物——小檗碱、巴马汀和药根碱——通过抑制脾酪氨酸激酶磷酸化来抑制 RBL-2H3 细胞脱颗粒。
FAHF-2 降低嗜碱性粒细胞和肥大细胞数量以及抑制 IgE 介导的肥大细胞激活可能有助于其对花生过敏的持续保护。