Human recombinant antimannan immunoglobulin G1 antibody confers resistance to hematogenously disseminated candidiasis in mice.
Human recombinant antimannan immunoglobulin G1 antibody confers resistance to hematogenously disseminated candidiasis in mice.
复制标题
人重组抗甘露聚糖免疫球蛋白 G1 抗体赋予小鼠对血源性念珠菌病的抵抗力。
DOI：
10.1128/iai.74.1.362-369.2006
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发表时间：
2006
影响因子：
3.1
通讯作者：
Kozel,ThomasR
中科院分区：
文献类型：
--
作者：
Zhang,MasonX;Bohlman,MCharlotte;Itatani,Carol;Burton,DennisR;Parren,PaulWHI;StJeor,StephenC;Kozel,ThomasR
甘露聚糖是植物细胞壁的主要成分。天然抗甘露聚糖抗体存在于大多数正常成人的血清中，但其在宿主抵抗血源性播散性念珠菌病中的作用尚不清楚。本研究的目的是制备重组人抗甘露聚糖抗体，并研究其保护作用。用白念珠菌细胞和化学纯化的甘露聚糖筛选噬菌体Fab展示组合文库。将一种称为M1的抗甘露聚糖Fab转化为全长免疫球蛋白G1抗体M1 g1，并在CHO细胞中产生M1 g1。在C.白色念珠菌血清型A和B、热带念珠菌、季也蒙念珠菌、光滑念珠菌和近平滑念珠菌。它的表达在23°C和37°C下都有活性，并且在细胞表面上均匀。用M1 g1被动免疫BALB/c小鼠，其对C.通过M1 g1剂量依赖性方式延长生存期（P，0.08至<0.001）和减少肾脏中感染灶的数量及其大小证明了这一点。体外研究发现M1 g1能促进C.小鼠腹腔巨噬细胞对白念珠菌细胞的吞噬作用是激活小鼠补体级联反应所必需的。因此，人抗甘露聚糖抗体可能在宿主抵抗系统性念珠菌病中具有保护作用。
Mannan is a major cell wall component found inCandidaspecies. Natural antimannan antibody is present in sera from most normal adults, but its role in host resistance to hematogenously disseminated candidiasis is unknown. The purpose of this study was to develop recombinant human antimannan antibody and to study its protective function. A phage Fab display combinatorial library containing Fab genes from bone marrow lymphocytes was screened withCandida albicansyeast cells and chemically purified mannan. One antimannan Fab, termed M1, was converted to a full-length immunoglobulin G1 antibody, M1g1, and M1g1 was produced in CHO cells. The M1g1 epitope was found inC. albicansserotypes A and B,Candida tropicalis,Candida guilliermondii,Candida glabrata, andCandida parapsilosis. Its expression was active at both 23°C and 37°C and uniform over the cell surface. BALB/c mice passively immunized with M1g1 were more resistant than control mice to a lethal hematogenous infection byC. albicans, as evidenced by extension of survival in an M1g1 dose-dependent manner (P, 0.08 to <0.001) and by reduction in number of infection foci and their size in the kidney. In vitro studies found that M1g1 promoted phagocytosis and phagocytic killing ofC. albicansyeast cells by mouse peritoneal macrophages and was required for activation of the mouse complement cascade. Thus, human antimannan antibody may have a protective role in host resistance to systemic candidiasis.