论文部分内容阅读
体外实验和动物实验证实,抗IgAFc受体I(FcαRI)单抗具有抑制炎症信号通路,治疗感染性疾病、改善免疫及非免疫相关肾脏疾病肾组织病变等作用。虽然早有研究证实抗FcαRI单抗的疗效与FcαRI中抑制性免疫受体酪氨酸激活基序(immunoreceptor tyrosine-based activation motifs,ITAM)介导的抑制性信号(ITAMi)有关,但直到近期ITAMi的分子机制才被阐明,即低亲和性配体或单克隆抗体与FcαRI结合后可促使FcαRI移位及含Src同源结构域2(Src homology 2,SH2)的酪氨酸磷酸酶1(SHP-1)在细胞膜脂质结构中募集,激活性受体与FcαRI等受体及SHP-1在细胞脂筏上的共区域化促进了大分子抑制体的形成,在SHP-1的作用下激活信号被抑制。这一机制的明确为IgAFcαRI单抗治疗肾脏疾病提供了新的理论依据。
In vitro and animal experiments confirmed that anti-IgAFc receptor I (FcαRI) monoclonal antibody can inhibit the inflammatory signaling pathway, the treatment of infectious diseases, improve immunity and non-immune renal disease related kidney disease and so on. Although early studies have demonstrated that the efficacy of anti-FcαRI monoclonal antibodies is related to the ITAMi-mediated inhibitory signal (ITAMi) in FcαRI, until the recent ITAMi The molecular mechanism was elucidated that binding of FcαRI to low-affinity ligands or monoclonal antibodies can promote FcαRI translocation and tyrosine phosphatase 1 (SH2) -containing Src homology 2 (SH2) SHP-1) recruits in the lipid membrane of the cell membrane. The co-localization of the activated receptor, FcαRI and other receptors and SHP-1 in the cell lipid rafts promotes the formation of macromolecular inhibitory substances. Under the action of SHP-1 The activation signal is suppressed. This mechanism clearly provides a new theoretical basis for IgAFc? RI monoclonal antibody treatment of kidney disease.