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Departments of
*
Biochemistry and
Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima, Japan;
Department of Biochemistry, Graduate School of Pharmaceutical Science, Hokkaido University, Sapporo, Japan; and
Department of Applied Biochemistry and Institute of Glycotechnology, Tokai University, Hiratsuka, Japan
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
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.
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