Turner Nancy A, Moake Joel L
Department of Bioengineering, Rice University, Houston, TX, USA.
Sci Rep. 2025 Mar 29;15(1):10883. doi: 10.1038/s41598-025-95533-6.
The immediate defense provided by the alternative complement pathway (AP) is under constant control by fluid phase regulators, factor H (FH) and factor I (FI), to prevent nonessential activation. Removal of either FI or FH from serum results in spontaneous AP activation, although the extent of activation caused by separate removal of each regulator has not been compared. In purified protein reactions with < 25% normal FH levels, additions of 6-100% normal FI levels, did not reduce C3a, Ba or FB cleavage. In reactions with 100% FH: C3a was not generated; Ba and FB cleavage was 3-fold lower; and C3 inactivation increased 2-fold as FI concentrations doubled. In reactions with 100% FI, FH levels ≥ 25% reduced C3a and Ba levels. AP activation levels were also compared in FI-depleted and FH-depleted serum. After magnesium addition to FI-depleted serum, C3a remained unchanged and Ba increased 3-fold, whereas in FH-depleted serum, C3a increased 13-fold and Ba increased 20-fold. Addition of 100% FI protein to FI-depleted serum did not change C3a and Ba, whereas, 100% FH added to FH-depleted serum prevented all activation. We conclude that normal levels of FH are sufficient to compensate for FI deficiencies and prevent unnecessary fluid phase AP activation.
替代补体途径（AP）提供的即时防御受到液相调节因子H因子（FH）和I因子（FI）的持续控制，以防止不必要的激活。从血清中去除FI或FH都会导致AP自发激活，不过尚未比较单独去除每种调节因子所引起的激活程度。在纯化蛋白反应中，当FH水平低于正常水平的25%时，添加6% - 100%正常水平的FI，并不会减少C3a、Ba或FB的裂解。在100% FH的反应中：不会产生C3a；Ba和FB的裂解降低3倍；随着FI浓度加倍，C3失活增加2倍。在100% FI的反应中，FH水平≥25%可降低C3a和Ba水平。还比较了FI缺失血清和FH缺失血清中的AP激活水平。向FI缺失血清中添加镁后，C3a保持不变，Ba增加3倍，而在FH缺失血清中，C3a增加13倍，Ba增加20倍。向FI缺失血清中添加100%的FI蛋白不会改变C3a和Ba，而向FH缺失血清中添加100%的FH可防止所有激活。我们得出结论，正常水平的FH足以补偿FI缺陷并防止不必要的液相AP激活。
