Recombinant form of human wild type mannan-binding lectin (MBL/A) but not its structural variant (MBL/C) promotes phagocytosis of zymosan by activating complement.
Recombinant form of human wild type mannan-binding lectin (MBL/A) but not its structural variant (MBL/C) promotes phagocytosis of zymosan by activating complement.
复制标题
人野生型甘露聚糖结合凝集素 (MBL/A) 的重组形式（MBL/A）而非其结构变体 (MBL/C) 通过激活补体促进酵母聚糖的吞噬作用。
DOI：
10.1016/j.molimm.2010.05.292
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发表时间：
2010
影响因子：
3.6
通讯作者：
Rawal,Nenoo
中科院分区：
文献类型：
--
作者：
Rajagopalan,Rema;Nyaundi,Takazvida;Salvi,VeenaP;Rawal,Nenoo
甘露聚糖结合凝集素（MBL）介导先天性免疫应答，如补体凝集素途径的激活和吞噬作用，以帮助对抗感染。在本研究中，采用重组形式的人MBL（rMBL），野生型MBL（rMBL/A）和其结构变异体rMBL/C在介导THP-1吞噬荧光标记的酵母聚糖的作用进行了检查，并比较从人血浆中纯化的MBL（pMBL/A）。流式细胞术分析显示，在MBL和经典途径组分C1 q（MBL/C1 q Dpl血清）均被耗尽的血清存在下，用rMBL/A和pMBL/A（0.5-30μg/ml）调理酵母聚糖导致THP-1细胞对其摄取的1.9倍和2.7倍增强。相反，用rMBL/C调理酵母聚糖时，没有观察到吞噬作用的增强。MBL单克隆抗体，EDTA，或甘露聚糖的调理反应混合物中添加抑制THP-1吞噬pMBL/A调理酵母聚糖。热灭活的MBL/C1 q Dpl血清取消了2倍的吞噬作用的增加，在没有血清的情况下，MBL的直接调理活性没有显着的酵母聚糖的摄取到THP-1细胞。补体成分C3和C4的活化产物沉积在用pMBL/A和rMBL/A调理的酵母聚糖上，但不沉积在用rMBL/C调理的酵母聚糖上，这表明MBL介导的酵母聚糖的吞噬作用需要补体凝集素途径的活化。这些发现意味着受损的MBL介导的吞噬作用可能会使突变等位基因MBL/C而不是野生型MBL/A的纯合子个体感染酵母菌等的风险增加。
Mannan-binding lectin (MBL) mediates innate immune responses, such as activation of the complement lectin pathway and phagocytosis, to help fight infections. In the present study, employing recombinant forms of human MBL (rMBL), the role of wild type MBL (rMBL/A) and its structural variant rMBL/C in mediating THP-1 phagocytosis of fluorescent-labeled zymosan was examined and compared to MBL purified from human plasma (pMBL/A). Flow cytometric analyses revealed that opsonization of zymosan with rMBL/A and pMBL/A (0.5–30μg/ml) resulted in a 1.9- and 2.7-fold enhancement in its uptake by THP-1 cells in the presence of serum that was depleted of both MBL and the classical pathway component, C1q (MBL/C1q Dpl serum). In contrast, no enhancement in phagocytosis was observed when zymosan was opsonized with rMBL/C. Addition of MBL monoclonal antibody, EDTA, or mannan to the opsonization reaction mixture inhibited THP-1 phagocytosis of pMBL/A opsonized zymosan. Heat inactivation of MBL/C1q Dpl serum abolished the 2-fold increase in phagocytosis and in the absence of serum the direct opsonic activity of MBL did not contribute significantly to the uptake of zymosan into THP-1 cells. Activation products of complement components C3 and C4 were deposited on zymosan opsonized with pMBL/A and rMBL/A but not rMBL/C indicating that MBL-mediated phagocytosis of zymosan requires activation of the complement lectin pathway. The findings imply that impaired MBL-mediated phagocytosis may put individuals homozygous for the mutant allele MBL/C but not wild type MBL/A at increased risk to infections such as yeast.