Studies on molecular constitution and effector functions of complement system

1.C4的构象变化：利用针对C4中新抗原的单克隆抗体，我们确定了C4中特定的疏水结构域，该结构域在C4被cs1激活后从内部部分暴露到表面。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、DAF和MCP-DAF杂交分子对人补体的调节作用进行了比较。杂化分子对补体替代途径具有加性保护作用，但对经典途径的保护作用不如单用DAF。组胺诱导DAF在人脐静脉内皮细胞（HUVEC）上的表达：10 mM组胺通过H_1受体使HUVEC上DAF的表达增强约2倍。这些结果表明，C5a过敏毒素从肥大细胞和嗜碱性细胞释放的组胺通过提高内皮细胞DAF的表达水平来增强内皮细胞的补体防御能力。过敏毒素C3a和C4a的生物学功能和受体。我们发现豚鼠巨噬细胞中存在两种类型的C3a受体，发现C3a受体介导的细胞反应被C4a下调。这些结果表明，与一般假设相反，C4a受体与C3a受体在功能上是不同的。

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.