Hakata Antigen, a New Member of the Ficolin/Opsonin p35 Family, Is a Novel Human Lectin Secreted into Bronchus/Alveolus and Bile

Abstract

SUMMARYHakata antigen was first reported as a serum protein that reacted with an autoantibody from patients with systemic lupus erythematosus. Recently, it has been found that Hakata antigen is a new member of the ficolin/opsonin p35 family, which is a distinct lectin family, on the basis of homology of structures and the common characteristic of possessing lectin activity. In this study we analyzed the tissue distribution of Hakata antigen. Hakata antigen mRNA and protein were generated in the lung and liver. In the lung, Hakata antigen was produced by both ciliated bronchial epithelial cells and Type II alveolar epithelial cells and was secreted into the bronchus and alveolus. In the liver, Hakata antigen was produced by bile duct epithelial cells and hepatocytes and was also secreted into the bile duct. These results demonstrate that Hakata antigen is a unique lectin protein that exists not only in serum but also in bronchus/alveolus and bile, and indicate that Hakata antigen plays a role in bronchus/alveolus and bile under physiological conditions. H akata antigen was first reported by Inaba and Okochi (1978) as a serum protein that reacted with an autoantibody from patients with systemic lupus erythematosus (SLE). Since then, it has been demonstrated that Hakata antigen is a novel thermolabile ␤ 2-macroglycoprotein that exists as a monomer of 35 kD in reducing conditions and as a huge homopolymer of 650 kD in serum or in nonreducing conditions (Yae et al. 1991). All sera from 10,050 healthy Japanese donors, 99.99% of 751,352 Japanese outpatients, and 99.98% of 41,430 Swedish outpatients contained Hakata antigen, showing that Hakata antigen is a normal serum constituent (Inaba et al. 1990). The range of Hakata antigen in serum was 7-23 g/ ml (Yae et al. 1991).We have recently identified the cDNA encoding Hakata antigen, revealing that Hakata antigen consists of a collagen-like domain in the middle section and a fibrinogen-like domain in the C terminus, both of which are homologous to two lectin activity-possessing proteins, human ficolin-1 and opsonin p35 (Sugimoto et al. 1998). Homologies between Hakata antigen and either human ficolin-1 or opsonin P35 were both 48% overall, higher in the collagen-like domain (48%, 54%) and in the fibrinogen-like domain (52%, 53%), respectively (Sugimoto et al. 1998). We have further demonstrated that purified Hakata antigen sustains lectin activity, showing affinity with GalNac, GlcNac, and d -fucose as mono/oligosaccharide, and LPSs from Salmonella typhimurium and S. minnesota (Sugimoto et al. 1998). These three molecules apparently form a distinct human lectin family. However, the physiological roles of these related molecules have remained unresolved. To date, porcine and mouse homologues of human ficolin-1 and opsonin p35 have been identified, whereas that of Hakata antigen has not been found (Ichijo et al.

Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas†

“…Ficolin 3 is expressed in hepatocytes and biliary cells and is excreted in the bile. 23,24 Ficolins are either secreted or attached to plasma membrane. They act as a site of aggregation of MASP proteases and are associated with the lectin pathway of complement activation.…”

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

“…Three types of ficolins have recently been identified in human, L-ficolin/P35 (FCN2 or ficolin 2) (12), M-ficolin (FCN1 or ficolin 1) (13,14), and H-ficolin/Hakata antigen (FCN3 or ficolin 3) (15)(16)(17), and two types of ficolins, ficolins A and B, have been identified in mice (18,19). The fibrinogen-like domain of L-ficolin, forming a globular structure like the CRD of MBL, is the pattern of carbohydrate structures.…”

Studies of the Pattern Recognition Molecule H-ficolin

“…Although similar in structure, H-ficolin (gi: 27754776) is quite different at the amino acid sequence level as compared with L-ficolin and M-ficolin with a sequence identity of only 45 and 46%, respectively. H-ficolin is synthesized by hepatocytes and bile duct epithelial cells where the protein is then secreted into the bloodstream and bile, respectively (25,26). H-ficolin is also found in the mucosa of the lung where it originates from bronchial epithelial cells and alveolar type II epithelial cells (25).…”

“…H-ficolin is synthesized by hepatocytes and bile duct epithelial cells where the protein is then secreted into the bloodstream and bile, respectively (25,26). H-ficolin is also found in the mucosa of the lung where it originates from bronchial epithelial cells and alveolar type II epithelial cells (25). The mean serum concentration of H-ficolin is 18.4 g/ml, as compared with 3.3 and 1.07 g/ml for L-and M-ficolin, respectively, and H-ficolin is thus the most abundant PRM of the lectin pathway (2,27).…”