Characterization of the interaction between serum mannan-binding protein and nucleic acid ligands.
Serum MBP, also known as MBL, is a C-type lectin that is known to be a soluble host defense factor involved in innate immunity. It has been well established that dying microbes and apoptotic cells release highly viscous DNA that induces inflammation and septic shock, and apoptotic cells display fragmented DNA on their surfaces. However, PRRs that mediate the recognition and clearance of free DNA and fragmented DNA in apoptotic cells have not been characterized clearly. Although MBP was reported recently to bind DNA as a novel ligand, binding characterization and the recognition implications have not been addressed yet. In this study, we show that MBP can bind DNA and RNA in a calcium-dependent manner from a variety of origins, including bacteria, plasmids, synthetic oligonucleotides, and fragmented DNA of apoptotic cells. Direct binding and competition studies indicate that MBP binds nucleic acids via its CRD to varying degrees and that MBP binds dsDNA more effectively than ssDNA and ssRNA. Furthermore, we reveal that the MBP-DNA complex does not trigger complement activation via the MBP lectin pathway, and the lectin pathway of complement activation is required for MBP-mediated enhancement of phagocytosis of targets bearing MBP ligands and that MBP can recognize the fragmented DNA presented on apoptotic cells. Therefore, we propose that the MBP lectin pathway may support effective recognition and clearance of cellular debris by facilitating phagocytosis, possibly through immunomodulatory mechanisms, thus preventing autoimmunity.
Nakamura
Natsuko
N
Research Center for Glycobiotechnology, Ritsumeikan University, Shiga 525-8577, Japan.
Nonaka
Motohiro
M
Ma
Bruce Yong
BY
Matsumoto
Shogo
S
Kawasaki
Nobuko
N
Asano
Shinji
S
Kawasaki
Toshisuke
T
D017209:Apoptosis / Q000235:genetics; D002241:Carbohydrates / Q000737:chemistry; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D037181:Lectins, C-Type / Q000378:metabolism; D008024:Ligands; D037601:Mannose-Binding Lectin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010587:Phagocytosis / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D044967:Serum / Q000378:metabolism; D020349:Surface Plasmon Resonance / Q000379:methods; D020298:U937 Cells
D002241:Carbohydrates; D037181:Lectins, C-Type; D008024:Ligands; D037601:Mannose-Binding Lectin; D012313:RNA; D004247:DNA