Kozel Thomas R, MacGill Randall S, Percival Ann, Zhou Qing
Department of Microbiology and Immunology and the Cell and Molecular Biology Program, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Infect Immun. 2004 Jan;72(1):209-18. doi: 10.1128/IAI.72.1.209-218.2004.
Sera from normal adult humans may contain high levels of antibody reactive with Candida albicans mannan. This study examined selected biological activities of such antibodies, focusing on sera that were collected from 34 donors and analyzed individually. The results showed that antimannan titers were normally distributed. Reactivity as determined by enzyme-linked immunosorbent assay with serotype A mannan generally paralleled reactivity with serotype B. Analysis of the kinetics for activation of the complement system and deposition of complement component 3 (C3) onto serotype A and serotype B cells showed a decrease in the lag time that occurred before the onset of rapid accumulation of C3 that correlated with increasing antimannan titers. In contrast, there was a decrease in the overall rate of accumulation of C3 on serotype A cells that was strongly correlated with increasing antibody titers; serotype B cells showed no such decrease. An evaluation of the contribution of mannan antibody to opsonophagocytic killing showed that mannan antibody in individual sera and antimannan immunoglobulin G (IgG) affinity purified from human plasma contributed to killing by neutrophils in a dose-dependent fashion in the absence of a functional complement system. However, affinity-purified antibody in very high concentrations was inhibitory to both complement-dependent and complement-independent opsonophagocytosis, and this finding suggests a prozone-like effect. In contrast, if the complement system was functional, antimannan IgG was not needed for opsonophagocytic killing. These results suggest that naturally occurring mannan antibodies and the complement system are functionally redundant for opsonophagocytic killing by neutrophils.
正常成年人的血清中可能含有高水平的与白色念珠菌甘露聚糖反应的抗体。本研究检测了此类抗体的特定生物学活性,重点关注从34名供体收集并单独分析的血清。结果表明,抗甘露聚糖滴度呈正态分布。通过酶联免疫吸附测定法测定的与A型甘露聚糖的反应性通常与与B型的反应性平行。对补体系统激活动力学以及补体成分3(C3)在A型和B型细胞上沉积的分析表明,在C3快速积累开始之前出现的延迟时间缩短,这与抗甘露聚糖滴度增加相关。相比之下,C3在A型细胞上的总体积累速率降低,这与抗体滴度增加密切相关;B型细胞则未出现这种降低。对甘露聚糖抗体对调理吞噬杀伤作用的贡献评估表明,个体血清中的甘露聚糖抗体以及从人血浆中亲和纯化的抗甘露聚糖免疫球蛋白G(IgG)在缺乏功能性补体系统的情况下以剂量依赖方式促进中性粒细胞的杀伤作用。然而,非常高浓度的亲和纯化抗体对补体依赖性和补体非依赖性调理吞噬作用均有抑制作用,这一发现提示存在前带样效应。相比之下,如果补体系统功能正常,调理吞噬杀伤作用则不需要抗甘露聚糖IgG。这些结果表明,天然存在的甘露聚糖抗体和补体系统在中性粒细胞的调理吞噬杀伤作用方面功能冗余。