Magee J C, Collins B H, Harland R C, Lindman B J, Bollinger R R, Frank M M, Platt J L
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Clin Invest. 1995 Nov;96(5):2404-12. doi: 10.1172/JCI118297.
Immunoglobulins regulate the complement system by activating complement on foreign surfaces and diverting reactive complement proteins away from autologous cell surfaces. Based on this model, we explored the ability of Ig to balance complement activation versus control in a pig-to-primate cardiac xenotransplantation model in which the binding of xenoreactive antibodies of the recipient to graft blood vessels and the activation of complement cause hyperacute rejection. Human IgG added to human serum caused a dose-dependent decrease in deposition of iC3b, cytotoxicity, and heparan sulfate release when the serum was incubated with porcine endothelial cells. This decrease was not caused by alteration in antibody binding or consumption of complement but presumably reflected decreased formation of C3 convertase on the endothelial cells. Infusion of purified human IgG into nonhuman primates prevented hyperacute rejection of porcine hearts transplanted into the primates. As expected, the transplants contained deposits of recipient Ig and C1q but not other complement components. The inhibition of complement on endothelial cell surfaces and in the xenotransplantation model supports the idea that IgG regulates the classical complement pathway and supports therapeutic use of that agent in humoral-mediated disease.
免疫球蛋白通过在异物表面激活补体并使反应性补体蛋白从自体细胞表面转移，从而调节补体系统。基于此模型，我们在猪到灵长类心脏异种移植模型中探索了免疫球蛋白平衡补体激活与控制的能力，在该模型中，受体的异种反应性抗体与移植血管的结合以及补体的激活会导致超急性排斥反应。当血清与猪内皮细胞孵育时，添加到人类血清中的人免疫球蛋白导致iC3b沉积、细胞毒性和硫酸乙酰肝素释放呈剂量依赖性降低。这种降低不是由抗体结合改变或补体消耗引起的，而是可能反映了内皮细胞上C3转化酶形成的减少。将纯化的人免疫球蛋白注入非人灵长类动物可防止移植到灵长类动物体内的猪心脏发生超急性排斥反应。正如预期的那样，移植组织中含有受体免疫球蛋白和C1q的沉积物，但没有其他补体成分。内皮细胞表面和异种移植模型中补体的抑制支持了免疫球蛋白调节经典补体途径的观点，并支持该药物在体液介导疾病中的治疗应用。
