Studies on molecular constitution and effector functions of complement system

1.C_4的构象变化：利用抗C_4中新抗原的单克隆抗体，我们确定了C_4中的一个特异性疏水结构域，该结构域在C_4被C_1s激活后从内部暴露到表面。2.补体系统调节因子的结构和功能：我们通过在中国仓鼠卵巢细胞上表达MCP、MCP-1和MCP-1杂合分子，比较了它们对人补体的调节作用。3.组胺诱导人脐静脉内皮细胞（human umbilical vein endothelial cells，HUVEC）表达H_1受体介导的H_2表达：10 mM组胺可使HUVEC表达H_1受体介导的H_2表达增加约2倍。这些结果提示，C5 a过敏毒素可使肥大细胞和嗜碱性粒细胞释放组胺，通过增加内皮细胞的组胺表达水平，增强内皮细胞的补体防御能力。4.过敏毒素C3 a和C4 a的生物学功能及其受体。我们已经揭示了豚鼠巨噬细胞上存在两种类型的C3 a受体，并发现C3 a受体介导的细胞反应被C4 a下调。这些结果表明，与一般假设相反，C4 a受体在功能上不同于C3 a受体。

1.A conformational change in C4 : Using monoclonal antibody against a neoantigen in C4, we have determined a specific hydrophobic domain in C4, which becomes exposed from interior portion to the surface upon activation of C4 by C1s.2.Structure and functions of regulatory factors of complement system : We have compared the regulatory effects of MCP, DAF, and MCP-DAF hybrid molecule against human complement by expressing the factors on Chinese hamster ovary cells. Hybrid molecule exerted additive protective effect against the alternative pathway of complement but was less potent in the classical pathway than DAF alone.3.Histamine-induced expression of DAF on human umbilical vein endothelial cells (HUVEC) : DAF expression on HUVEC was found to be enhanced about 2 fold with 10 mM histamine through H_1 receptor. These results suggest that histamine, which is released from mast cells and basophils by C5a anaphylatoxin, increases the complement defense ability of endothelial cells by increaseing their levels of DAF expression.4.Biological functions and receptors of anaphylatoxins, C3a and C4a. We have revealed the presence of two types of C3a receptor on guinea pig macrophages and found that C3a receptor-mediated cellular responses are down-regulated by C4a. These results suggest that contrary to general assumption, C4a receptor is functionally different from C3a receptor.