Liu Yu, Endo Yuichi, Iwaki Daisuke, Nakata Munehiro, Matsushita Misao, Wada Ikuo, Inoue Keiichi, Munakata Mitsuru, Fujita Teizo
Department of Immunology, Institute of Biomedical Sciences, Fukushima Medical University, 1-Hikarigaoka, Japan.
J Immunol. 2005 Sep 1;175(5):3150-6. doi: 10.4049/jimmunol.175.5.3150.
Three types of ficolins have been identified in humans: L-ficolin, M-ficolin, and H-ficolin. Similar to mannose-binding lectin, L-ficolin and H-ficolin are the recognition molecules in the lectin complement pathway. Another human ficolin, M-ficolin, is a nonserum ficolin that is expressed in leukocytes and lung; however, little is known about its physiologic roles. In this study, we report the characterization of M-ficolin in terms of its protein localization and lectin activity. M-ficolin was localized in secretory granules in the cytoplasm of neutrophils, monocytes, and type II alveolar epithelial cells in lung. M-ficolin precipitated with mannose-binding lectin-associated serine proteases (MASP)-1 and MASP-2 in a co-immunoprecipitation assay, indicating that M-ficolin forms complexes with MASP-1 and MASP-2. M-ficolin-MASP complexes activated complement on N-acetylglucosamine (GlcNAc)-coated microplates in a C4 deposition assay. M-ficolin bound to several neoglycoproteins bearing GlcNAc, N-acetylgalactosamine, and sialyl-N-acetyllactosamine, suggesting that M-ficolin can recognize the common carbohydrate residues found in microbes. Indeed, M-ficolin bound to Staphylococcus aureus through GlcNAc. These results indicate that M-ficolin, like its family members, functions as a recognition molecule of the lectin complement pathway and plays an important role in innate immunity.
L-纤维胶凝蛋白、M-纤维胶凝蛋白和H-纤维胶凝蛋白。与甘露糖结合凝集素相似，L-纤维胶凝蛋白和H-纤维胶凝蛋白是凝集素补体途径中的识别分子。另一种人类纤维胶凝蛋白M-纤维胶凝蛋白是一种在白细胞和肺中表达的非血清纤维胶凝蛋白；然而，对其生理作用知之甚少。在本研究中，我们报告了M-纤维胶凝蛋白在蛋白质定位和凝集素活性方面的特征。M-纤维胶凝蛋白定位于肺中嗜中性粒细胞、单核细胞和II型肺泡上皮细胞细胞质中的分泌颗粒中。在共免疫沉淀试验中，M-纤维胶凝蛋白与甘露糖结合凝集素相关丝氨酸蛋白酶（MASP）-1和MASP-2沉淀，表明M-纤维胶凝蛋白与MASP-1和MASP-2形成复合物。在C4沉积试验中，M-纤维胶凝蛋白-MASP复合物在N-乙酰葡糖胺（GlcNAc）包被的微孔板上激活补体。M-纤维胶凝蛋白与几种带有GlcNAc、N-乙酰半乳糖胺和唾液酸-N-乙酰乳糖胺的新糖蛋白结合，表明M-纤维胶凝蛋白可以识别微生物中常见的碳水化合物残基。事实上，M-纤维胶凝蛋白通过GlcNAc与金黄色葡萄球菌结合。这些结果表明，M-纤维胶凝蛋白与其家族成员一样，作为凝集素补体途径的识别分子，在先天免疫中发挥重要作用。
