Mannan-specific immunoglobulin G antibodies in normal human serum accelerate binding of C3 to Candida albicans via the alternative complement pathway.

Mannan-specific immunoglobulin G antibodies in normal human serum accelerate binding of C3 to Candida albicans via the alternative complement pathway.
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正常人血清中的甘露聚糖特异性免疫球蛋白 G 抗体可通过替代补体途径加速 C3 与白色念珠菌的结合。

DOI:
10.1128/iai.66.10.4845-4850.1998
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发表时间:
1998
影响因子:
3.1
通讯作者:
Kozel,TR
Kozel,TR
中科院分区:
医学2区
文献类型:
--
作者:
Zhang,MX;Kozel,TR

文献摘要

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白色念珠菌激活经典和替代补体途径,导致调理素补体片段沉积在细胞表面。我们以前的研究发现,正常人血清(NHS)中的抗甘露聚糖免疫球蛋白G(IgG)允许C。白色念珠菌启动经典途径。本研究的目的是确定抗甘露聚糖IgG是否也在旁路途径的启动中发挥作用。通过单独或与抗甘露聚糖抗体的免疫亲和去除组合用EGTA螯合血清Ca2+,使合并的NHS不含经典途径活性。动力学分析表明,在检测C3结合到C的6分钟滞后。与EGTA螯合和甘露聚糖吸收的NHS中的12分钟滞后相比,在EGTA螯合的NHS中,白念珠菌被取代。通过加入亲和纯化的抗甘露聚糖IgG,12分钟的滞后缩短至6分钟。抗甘露聚糖IgG对旁路途径起始的加速作用是剂量依赖性的,并且在由旁路途径的六种纯化蛋白组成的补体结合反应中再现。抗甘露聚糖IgG的Fab和F(ab ′)2片段均以与完整抗体相似的方式促进旁路途径的启动。免疫荧光分析表明,除了抗甘露聚糖IgG EGTA螯合和甘露聚糖吸收的血清促进了早期沉积的C3分子的酵母细胞上,但有很少或没有影响的分布的细胞网站C3激活。因此,抗甘露聚糖IgG抗体在宿主补体系统与C之间的相互作用中发挥重要的调节作用。白色念珠菌。
Candida albicansactivates the classical and alternative complement pathways, leading to deposition of opsonic complement fragments on the cell surface. Our previous studies found that antimannan immunoglobulin G (IgG) in normal human serum (NHS) allowsC. albicansto initiate the classical pathway. The purpose of this study was to determine whether antimannan IgG also plays a role in initiation of the alternative pathway. Pooled NHS was rendered free of classical pathway activity by chelation of serum Ca2+with EGTA alone or in combination with immunoaffinity removal of antimannan antibodies. Kinetic analysis revealed a 6-min lag in detection of C3 binding toC. albicansincubated in EGTA-chelated NHS, compared to a 12-min lag in NHS that was both EGTA chelated and mannan absorbed. The 12-min lag was shortened to 6 min by addition of affinity-purified antimannan IgG. The accelerating effect of antimannan IgG on alternative pathway initiation was dose dependent and was reproduced in a complement binding reaction consisting of six purified proteins of the alternative pathway. Both Fab and F(ab′)2fragments of antimannan IgG facilitated alternative pathway initiation in a manner similar to that observed with intact antibody. Immunofluorescence analysis showed that addition of antimannan IgG to EGTA-chelated and mannan-absorbed serum promoted an early deposition of C3 molecules on the yeast cells but had little or no effect on distribution of the cellular sites for C3 activation. Thus, antimannan IgG antibodies play an important regulatory role in interactions between the host complement system andC. albicans.