Here we present an in vitro model of AP activation and regulation on a glycomatrix surface. We use an extracellular matrix substitute (MaxGel) as a base upon which we reconstitute AP C3 convertase. We validated this method using properdin and Factor H (FH) and then assessed the effects of genetic and acquired drivers of C3G on C3 convertase.
We show that C3 convertase readily forms on MaxGel and that this formation was positively regulated by properdin and negatively regulated by FH. Additionally, Factor B (FB) and FH mutants impaired complement regulation when compared to wild type counterparts. We also show the effects of C3 nephritic factors (C3Nefs) on convertase stability over time and provide evidence for a novel mechanism of C3Nef-mediated C3G pathogenesis.
We conclude that this ECM-based model of C3G offers a replicable method by which to evaluate the variable activity of the complement system in C3G, thereby offering an improved understanding of the different factors driving this disease process.
UNASSIGNED:在这里,我们提出了在糖基质表面上AP激活和调节的体外模型。
UNASSIGNED:我们表明C3转化酶容易在MaxGel上形成,并且这种形成受备解素正调节,受FH负调节。
UNASSIGNED:我们得出结论,这种基于ECM的C3G模型提供了一种可复制的方法,通过该方法可以评估C3G中补体系统的可变活性,