1-Fluoro-2,4-dinitrobenzene and its derivatives act as secretagogues on rodent mast cells.
1-Fluoro-2,4-dinitrobenzene and its derivatives act as secretagogues on rodent mast cells.
复制标题
1-氟-2,4-二硝基苯及其衍生物可作为啮齿动物肥大细胞的促分泌剂。
DOI：
10.1002/eji.201646536
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
S.
中科院分区：
文献类型：
--
作者：
Manabe;Y.;Yoshimura;M.;Sakamaki;K.;Inoue;A.;Kakinoki;A.;Hokari;S.;Sakanaka;M.;Aoki;J.;Miyachi;H.;Furuta;K.;and Tanaka;S.
越来越多的证据表明，活化的肥大细胞参与接触性超敏反应，尽管其活化的确切机制仍不完全清楚。我们使用小鼠骨髓来源的培养肥大细胞和大鼠腹膜肥大细胞研究了常见实验性过敏原诱导肥大细胞活化的潜力。在这些过敏原中，发现1-氯-2，4-二硝基苯和1-氟-2，4-二硝基苯（DNFB）可诱导大鼠腹腔肥大细胞脱颗粒。DNFB诱导的脱粒伴随着胞质Ca 2+动员，并被百日咳毒素、U 73122（一种磷脂酶C抑制剂）和BAPTA（一种Ca 2+螯合剂）显著抑制，这增加了DNFB作用于G蛋白偶联受体并激活Gi的可能性，Gi诱导磷脂酶C以及已知的肥大细胞促分泌素（如化合物48/80）的激活。在无血清蛋白和IgE的情况下，DNFB可诱导肥大细胞脱颗粒。构效关系分析表明，脱颗粒的程度和DNFB衍生物的C1碳的电子密度之间呈负相关。这些发现提出了一种可能性，DNFB作为一个有效的接触过敏原，通过诱导皮肤肥大细胞脱粒。
Accumulating evidence suggests that activated mast cells are involved in contact hypersensitivity, although the precise mechanisms of their activation are still not completely understood. We investigated the potential of common experimental allergens to induce mast cell activation using murine bone marrow‐derived cultured mast cells and rat peritoneal mast cells. Among these allergens, 1‐chloro‐2,4‐dinitrobenzene and 1‐fluoro‐2,4‐dinirobenzene (DNFB) were found to induce degranulation of rat peritoneal mast cells. DNFB‐induced degranulation is accompanied by cytosolic Ca2+mobilization and is significantly inhibited by pertussis toxin, U73122 (a phospholipase C inhibitor), and BAPTA (a Ca2+chelator), raising the possibility that DNFB acts on the G protein‐coupled receptors and activates Gi, which induces activation of phospholipase C, as well as known mast cell secretagogues, such as compound 48/80. DNFB could induce mast cell degranulation in the absence of serum proteins and IgE. Structure‐activity relationship analyses revealed an inverse correlation between the degree of degranulation and the electron density of the C1 carbon of the DNFB derivatives. These findings raise a possibility that DNFB functions as a potent contact allergen through induction of cutaneous mast cell degranulation.