An ancient lectin-dependent complement system in an ascidian: novel lectin isolated from the plasma of the solitary ascidian, Halocynthia roretzi.
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.
Sekine
H
H
Department of Biochemistry and Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima, Japan.
Kenjo
A
A
Azumi
K
K
Ohi
G
G
Takahashi
M
M
Kasukawa
R
R
Ichikawa
N
N
Nakata
M
M
Mizuochi
T
T
Matsushita
M
M
Endo
Y
Y
Fujita
T
T
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*
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