Clarification of the origin of the classical complement pathway

经典的补体途径是通过C1q与免疫复合物结合而激活的。另一方面，凝集素补体途径是通过凝集素与病原体表面的碳水化合物结合而激活的，而无需免疫球蛋白的参与。凝集素和经典途径分别存在于海鞘和软骨鱼类以上的动物中。七鳃鳗属于最原始的脊椎动物，其血清凝集素（LC1q）与哺乳动物的Clq结构相似。这一事实表明，凝集素途径进化为经典途径。本课题旨在分析低等动物的LC1q和凝集素，以阐明经典途径的起源。我们得到了以下发现。1、七鳃鳗有三种类型的MASP （MASP- a、MASP- b和MASP-1）。LC1q被发现与MASP-1和MASP-A络合。2、LC1q是n -乙酰氨基葡萄糖（GlcNAc）特异性凝集素。LC - lq-MASP复合物与GlcNAc5-DPPE（新糖脂）结合后，复合物激活七鳃鳗C3.3， Anti-MASP-1抗体在液相中抑制lc1q - masp介导的七鳃鳗C3活化。4、从杖海鞘血浆中分离到glcnac结合凝集素。该凝集素制剂具有丝氨酸蛋白酶活性。凝集素经胶原酶处理后，其分子大小变为哺乳动物C1q的gC1q结构域。

The classical complement pathway is activated by binding of C1q to immune complexes. On the other hand, the lectin complement pathway is activated by binding of lectins to carbohydrates on the surfaces of pathogens without involvement of immunoglobulins. The lectin and classical pathways are present in animals above ascidians and cartilaginous fishes, respectively. Lamprey belongs to agnathans, the most primitive vertebrates, and has a serum lectin (LC1q) with having a structural similarity to mammalian Clq. This fact suggests that the lectin pathway evolved to the classical pathway. The aim of this research project was to analyze LC1q and lectins in lower animals so as to clarify the origin of the classical pathway. We obtained the following findings.1,Lamprey has three types of MASP (MASP-A, MASP-B and MASP-1). LC1q was found to be complexed with MASP-1 as well as MASP-A.2, LC1q is a lectin specific for N-acetylglucosamine (GlcNAc). Upon binding of the LC lq-MASP complex to GlcNAc5-DPPE (neoglycolipid), the complex activated lamprey C3.3, Anti-MASP-1 antibodies inhibited LC1q-MASP-mediated lamprey C3 activation in the fluid phase.4, A GlcNAc-binding lectin was isolated from plasma of Styela clava. The lectin preparations had a serine protease activity. After treatment of the lectin with collagenase, its molecular size changed to that of gC1q domain of mammalian C1q.