Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement
Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement
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DOI：
10.1074/jbc.m400701200
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发表时间：
2004-06-11
影响因子：
4.8
通讯作者：
Lee, BL
中科院分区：
文献类型：
--
作者：
Ma, YG;Cho, MY;Lee, BL
脊椎动物和无脊椎动物的先天免疫反应需要模式识别受体或蛋白质的存在，这些受体或蛋白质识别微生物细胞成分，包括内毒素、细菌肽聚糖(PGN)和真菌1，3-β-D-葡聚糖。我们以前报道过昆虫血淋巴中的PGN和1，3-β-D-葡聚糖识别蛋白能够诱导酚氧化酶原激活系统的激活，这是无脊椎动物的主要先天免疫反应之一。这项研究的目的是描述这些分子的生物化学特性和人类对应物的影响。从人血清中分离纯化了可溶性模式识别蛋白，鉴定为甘露糖结合凝集素和L-无花果胶体。利用特定的微生物细胞组分偶联柱证实MBL和L-无花果苷分别与PGN和1，3-β-D-葡聚糖结合。Western印迹分析表明，纯化的MBL和L无花果蛋白与MBL相关丝氨酸蛋白酶-1和-2(MASPs)和小分子MBL相关蛋白结合。最后，纯化的MBL/MASP和L-无花果林/MASP分别与PGN和1，3-β-D-葡聚糖结合，导致凝集素-补体途径的激活。这些结果表明，人PGN和1，3-β-D-葡聚糖识别蛋白作为补体激活凝集素发挥作用。
The innate immune response in vertebrates and invertebrates requires the presence of pattern recognition receptors or proteins that recognize microbial cell components including lipopolysaccharide, bacterial peptidoglycan (PGN), and fungal 1,3-beta-D-glucan. We reported previously that PGN and 1,3-beta-D-glucan recognition proteins from insect hemolymph were able to induce the activation of the prophenoloxidase-activating system, one of the major invertebrate innate immune reactions. The goal of this study was to characterize the biochemical properties and effects of the human counterparts of these molecules. Soluble pattern recognition proteins were purified from human serum and identified as human mannose-binding lectin (MBL) and L-ficolin. The use of specific microbial cell component-coupled columns demonstrated that MBL and L-ficolin bind to PGN and 1,3-beta-D-glucan, respectively. Purified MBL and L-ficolin were associated with MBL-associated serine proteases-1 and -2 (MASPs) and small MBL-associated protein as determined by Western blot analysis. Finally, the binding of purified MBL/MASP and L-ficolin/MASP complexes to PGN and 1,3-beta-D-glucan, respectively, resulted in the activation of the lectin-complement pathway. These results indicate that human PGN and 1,3-beta-D-glucan recognition proteins function as complement-activating lectins.