title: An ancient lectin-dependent complement system in an ascidian: novel lectin isolated from the plasma of the solitary ascidian, Halocynthia roretzi.
abstract: Mannose-binding lectin (MBL) is a C-type lectin involved in the first line of host defense against pathogens and it requires MBL-associated serine protease (MASP) for activation of the complement lectin pathway. To elucidate the origin and evolution of MBL, MBL-like lectin was isolated from the plasma of a urochordate, the solitary ascidian Halocynthia roretzi, using affinity chromatography on a yeast mannan-Sepharose. SDS-PAGE of the eluted proteins revealed a major band of approximately 36 kDa (p36). p36 cDNA was cloned from an ascidian hepatopancreas cDNA library. Sequence analysis revealed that the carboxy-terminal half of the ascidian lectin contains a carbohydrate recognition domain (CRD) that is homologous to C-type lectin, but it lacks a collagen-like domain that is present in mammalian MBLs. Purified p36 binds specifically to glucose but not to mannose or N-acetylglucosamine, and it was designated glucose-binding lectin (GBL). The two ascidian MASPs associated with GBL activate ascidian C3, which had been reported to act as an opsonin. The removal of GBL-MASPs complex from ascidian plasma using Ab against GBL inhibits C3-dependent phagocytosis. These observations strongly suggest that GBL acts as a recognition molecule and that the primitive complement system, consisting of the lectin-proteases complex and C3, played a major role in innate immunity before the evolution of an adaptive immune system in vertebrates.
authors.affiliation: Department of Biochemistry and Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sekine
authors.forename: A
authors.initials: A
authors.lastname: Kenjo
authors.forename: K
authors.initials: K
authors.lastname: Azumi
authors.forename: G
authors.initials: G
authors.lastname: Ohi
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: R
authors.initials: R
authors.lastname: Kasukawa
authors.forename: N
authors.initials: N
authors.lastname: Ichikawa
authors.forename: M
authors.initials: M
authors.lastname: Nakata
authors.forename: T
authors.initials: T
authors.lastname: Mizuochi
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D037222:Collectins; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D004064:Digestive System; D019143:Evolution, Molecular; D015723:Gene Library; D037102:Lectins / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism; D014561:Urochordata / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D037222:Collectins; D003176:Complement C3; D037102:Lectins; C440025:lectin 36 kDa, Halocynthia roretzi; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases