Suzukawa Maho, Komiya Akiko, Yoshimura-Uchiyama Chitose, Kawakami Ayako, Koketsu Rikiya, Nagase Hiroyuki, Iikura Motoyasu, Yamada Hirokazu, Ra Chisei, Ohta Ken, Yamamoto Kazuhiko, Yamaguchi Masao
Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Int Arch Allergy Immunol. 2007;143 Suppl 1:56-9. doi: 10.1159/000101406. Epub 2007 May 1.
Surface-expressed CD69 is a recently recognized activation marker for basophils and is reported to be strongly induced in vitro by IL-3. In this study, we investigated whether IgE- and high-affinity receptor for IgE (FcepsilonRI)-dependent stimuli can affect basophil CD69 expression. Highly purified basophils were cultured for 24 h in the presence of anti-FcepsilonRI alpha-chain mAb, CRA-1 and IL-3, and surface CD69 expression was analyzed by flow cytometry. CRA-1 mAb at 1 ng/ml or lower concentrations, levels too low to provoke direct histamine release, dose-dependently enhanced surface CD69 expression in the presence of IL-3, although low-dose CRA-1 mAb failed to induce CD69 expression in the absence of IL-3. Recombinant Der f 2 at 10 to 100 pg/ml enhanced CD69 levels in the presence of IL-3 in basophils from mite-sensitive subjects. These results suggest that allergens may influence basophil CD69 expression even when the levels of the antigens are too low to trigger direct degranulation. Upregulated CD69 expression on locally accumulated basophils in bronchial asthma may be attributed at least in part to a combination of local cytokines, especially IL-3, plus exposure to low levels of IgE-crosslinking allergens.
表面表达的CD69是一种最近被认可的嗜碱性粒细胞激活标志物,据报道在体外可被IL-3强烈诱导。在本研究中,我们调查了IgE和IgE高亲和力受体(FcepsilonRI)依赖性刺激是否会影响嗜碱性粒细胞CD69的表达。将高度纯化的嗜碱性粒细胞在抗FcepsilonRIα链单克隆抗体CRA-1和IL-3存在的情况下培养24小时,并通过流式细胞术分析表面CD69的表达。浓度为1 ng/ml或更低的CRA-1单克隆抗体,其水平过低以至于无法引发直接的组胺释放,在IL-3存在的情况下剂量依赖性地增强了表面CD69的表达,尽管低剂量的CRA-1单克隆抗体在没有IL-3的情况下未能诱导CD69的表达。10至100 pg/ml的重组Der f 2在IL-3存在的情况下增强了螨敏感受试者嗜碱性粒细胞中的CD69水平。这些结果表明,即使抗原水平过低而无法触发直接脱颗粒作用,变应原也可能影响嗜碱性粒细胞CD69的表达。支气管哮喘中局部积聚的嗜碱性粒细胞上CD69表达上调可能至少部分归因于局部细胞因子(尤其是IL-3)与低水平IgE交联变应原暴露的共同作用。