首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Increased survival and reduced renal injury in MRL/lpr mice treated with a human Fcγ receptor II (CD32) peptide
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Increased survival and reduced renal injury in MRL/lpr mice treated with a human Fcγ receptor II (CD32) peptide

机译:用人Fcγ受体II(CD32)肽治疗的MRL / lpr小鼠的存活率提高且肾损伤减少

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摘要

Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease affecting many organs. The deposition in kidney tissue of immune complexes and their interaction with macrophages is thought to trigger the inflammatory response leading to glomerulonephritis. It has been demonstrated that inhibition of this interaction in murine models can alleviate the disease. Six synthetic peptides were derived from the membrane-proximal extracellular domain (EC2) of human Fcγ receptor II (huFcγRII). Of these, one peptide, huRII6, was shown to be a potent competitive inhibitor of IgG binding to recombinant FcγRII in vitro. To examine the possible therapeutic impact of huRII6 in vivo, this peptide, or a control, was given by subcutaneous injection to female MRL/lpr mice from weeks 7 to 36, resulting in an enhanced survival rate compared with control-treated animals and a reduction of proteinuria. Histopathological examination of the kidneys showed a reduction in deposition of immune complexes and preservation of structure. Such a functional peptide should prove useful for examining the role of IgG-FcγR interactions in experimental models of disease and may provide for the development of FcR-targeting drugs to treat autoimmune disorders.
机译:系统性红斑狼疮(SLE)是一种影响许多器官的多系统慢性炎症性疾病。免疫复合物在肾组织中的沉积及其与巨噬细胞的相互作用被认为会引发导致肾小球肾炎的炎症反应。已经证明在鼠模型中抑制这种相互作用可以减轻该疾病。六个合成肽衍生自人Fcγ受体II(huFcγRII)的近膜细胞外结构域(EC2)。其中,一种肽huRII6被证明是与重组FcγRII结合的IgG的有效竞争抑制剂。为了检查huRII6在体内的可能的治疗作用,通过皮下注射从第7周到第36周对雌性MRL / lpr小鼠给予此肽或对照,与对照组相比,存活率提高了,并且降低了蛋白尿。肾脏的组织病理学检查显示免疫复合物沉积减少,结构得以保留。这种功能性肽应被证明可用于检查疾病实验模型中IgG-FcγR相互作用的作用,并可为开发靶向FcR的药物以治疗自身免疫性疾病提供帮助。

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