Isolation, cloning, and characterization of a novel phosphomannan-binding lectin from porcine serum.
Mannan-binding protein (MBP) is a C-type serum lectin that is an important constituent of the innate immune defense because it activates the complement system via the lectin pathway. While the pig has been proposed to be an attractive source of xenotransplantable tissues and organs, little is known about porcine MBP. In our previous studies, phosphomannan, but not mannan, was found to be an effective inhibitor of the C1q-independent bactericidal activity of newborn piglet serum against some rough strains of Gram-negative bacteria. In contrast, the inhibitory activities of phosphomannan and mannan were very similar in the case of MBP-dependent bactericidal activity against rough strains of Escherichia coli K-12 and S-16. Based on these findings, we inferred that an MBP-like lectin with slightly or completely different carbohydrate binding specificity might exist in newborn piglet serum and be responsible for the C1q-independent bactericidal activity. Herein we report that a novel phosphomannan-binding lectin (PMBL) of 33 kDa under reducing conditions was isolated from both newborn and adult porcine serum and characterized. Porcine PMBL functionally activated the complement system via the lectin pathway triggered by binding with both phosphomannan (P-mannan) and mannan, which, unlike MBP, was effectively inhibited by mannose 6-phosphate- or galatose-containing oligosaccharides. Our observations suggest that porcine PMBL plays a critical role in the innate immune defense from the newborn stage to adult-hood, and the establishment of a newborn piglet experimental model for the innate immune system studies is a valuable step toward elucidation of the physiological function and molecular mechanism of lectin pathway.
Ma
Bruce Yong
BY
Research Center for Glycobiotechnology, Ritsumeikan University, Shiga 525-8577, Japan. byma@fc.ritsumei.ac.jp
Nakamura
Natsuko
N
Dlabac
Vladimir
V
Naito
Haruna
H
Yamaguchi
Shinsuke
S
Ishikawa
Makiko
M
Nonaka
Motohiro
M
Ishiguro
Masaji
M
Kawasaki
Nobuko
N
Oka
Shogo
S
Kawasaki
Toshisuke
T
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D003001:Cloning, Molecular; D015922:Complement C1q / Q000276:immunology; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics*; D048168:Escherichia coli K12 / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics*; D037181:Lectins, C-Type / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D008351:Mannans / Q000276:immunology; D008969:Molecular Sequence Data; D044967:Serum / Q000737:chemistry / Q000378:metabolism; D013552:Swine
D037181:Lectins, C-Type; D008351:Mannans; D015922:Complement C1q; C005437:phosphomannan