Cloning and characterization of mannose-binding lectin from lamprey (Agnathans).
The recognition of pathogens is mediated by a set of pattern recognition molecules that recognize conserved pathogen-associated molecular patterns shared by broad classes of microorganisms. Mannose-binding lectin (MBL) is one of the pattern recognition molecules and activates complement in association with MBL-associated serine protease (MASP) via the lectin pathway. Recently, an MBL-like lectin was isolated from the plasma of a urochordate, the solitary ascidian. This ascidian lectin has a carbohydrate recognition domain, but the collagen-like domain was replaced by another sequence. To elucidate the origin of MBLs, the aim of this study is to determine the structure and function of the MBL homolog in lamprey, the most primitive vertebrate. Using an N-acetylglucosamine (GlcNAc)-agarose column, MBL-like lectin (p25) was isolated from lamprey serum and cDNA cloning was conducted. From the deduced amino acid sequence this lectin has a collagenous region and a typical carbohydrate recognition domain. This lectin also binds mannose, glucose, and GlcNAc, but not galactose, indicating that it is structurally and functionally similar to the mammalian MBLs. Furthermore, it associated with lamprey MASPs, and the MBL-MASP activated lamprey C3 in fluid-phase and on the surface of pathogens. In conjunction with the phylogenetic analysis, it seems likely that the lamprey MBL is an ortholog of the mammalian MBL. Because acquired immunity seems to have been established only from jawed vertebrates onward, the lectin complement pathway in lamprey, as one of the major contributors to innate immunity, plays a pivotal role in defending the body against microorganisms.
Department of Immunology, Fukushima Medical University, Fukushima, Japan.
Momoe
M
Takahashi
Daisuke
D
Iwaki
Akiko
A
Matsushita
Munehiro
M
Nakata
Misao
M
Matsushita
Yuichi
Y
Endo
Teizo
T
Fujita
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D050260:Carbohydrate Metabolism; D003001:Cloning, Molecular; D003176:Complement C3 / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D007798:Lampreys / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
D003176:Complement C3; D018076:DNA, Complementary; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases