Human M-ficolin is a secretory protein that activates the lectin complement pathway.
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.
Liu
Yu
Y
Department of Immunology, Institute of Biomedical Sciences, Fukushima Medical University, 1-Hikarigaoka, Japan.
Endo
Yuichi
Y
Iwaki
Daisuke
D
Nakata
Munehiro
M
Matsushita
Misao
M
Wada
Ikuo
I
Inoue
Keiichi
K
Munakata
Mitsuru
M
Fujita
Teizo
T
D003167:Complement Activation; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D037601:Mannose-Binding Lectin / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases; D013211:Staphylococcus aureus / Q000378:metabolism; D000097604:Ficolins
D006001:Glycoconjugates; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D000097604:Ficolins; C084067:MASP1 protein, human; C105296:MASP2 protein, human