Clarification of the origin of the classical complement pathway

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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.