Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement.
The innate immune response in vertebrates and invertebrates requires the presence of pattern recognition receptors or proteins that recognize microbial cell components including lipopolysaccharide, bacterial peptidoglycan (PGN), and fungal 1,3-beta-D-glucan. We reported previously that PGN and 1,3-beta-D-glucan recognition proteins from insect hemolymph were able to induce the activation of the prophenoloxidase-activating system, one of the major invertebrate innate immune reactions. The goal of this study was to characterize the biochemical properties and effects of the human counterparts of these molecules. Soluble pattern recognition proteins were purified from human serum and identified as human mannose-binding lectin (MBL) and L-ficolin. The use of specific microbial cell component-coupled columns demonstrated that MBL and L-ficolin bind to PGN and 1,3-beta-D-glucan, respectively. Purified MBL and L-ficolin were associated with MBL-associated serine proteases-1 and -2 (MASPs) and small MBL-associated protein as determined by Western blot analysis. Finally, the binding of purified MBL/MASP and L-ficolin/MASP complexes to PGN and 1,3-beta-D-glucan, respectively, resulted in the activation of the lectin-complement pathway. These results indicate that human PGN and 1,3-beta-D-glucan recognition proteins function as complement-activating lectins.
Ma
Young Gerl
YG
College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan 609-735, Korea.
Cho
Mi Yhang
MY
Zhao
Mingyi
M
Park
Ji Won
JW
Matsushita
Misao
M
Fujita
Teizo
T
Lee
Bok Luel
BL
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000302:isolation & purification / Q000502:physiology*; D037582:Complement Pathway, Mannose-Binding Lectin; D005936:Glucans / Q000378:metabolism; D006801:Humans; D037102:Lectins; D037601:Mannose-Binding Lectin / Q000302:isolation & purification / Q000502:physiology*; D050606:Mannose-Binding Protein-Associated Serine Proteases; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000378:metabolism; D012697:Serine Endopeptidases / Q000502:physiology; D047071:beta-Glucans; D000097604:Ficolins
D002352:Carrier Proteins; D005936:Glucans; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D010457:Peptidoglycan; D012697:Serine Endopeptidases; D047071:beta-Glucans; D000097604:Ficolins; C033363:beta-1,3-glucan