Mannose-binding lectin: targeting the microbial world for complement attack and opsonophagocytosis

Citation
Dl. Jack et al., Mannose-binding lectin: targeting the microbial world for complement attack and opsonophagocytosis, IMMUNOL REV, 180, 2001, pp. 86-99
Citations number
98
Categorie Soggetti
Immunology
Journal title
IMMUNOLOGICAL REVIEWS
ISSN journal
01052896 → ACNP
Volume
180
Year of publication
2001
Pages
86 - 99
Database
ISI
SICI code
0105-2896(200104)180:<86:MLTTMW>2.0.ZU;2-S
Abstract
Mannose-binding lectin (MBL) is an important constituent-of the innate immu ne system. This protein binds through multiple lectin domains to the repeat ing sugar arrays that decorate many microbial:surfaces, and is then able to activate the complement system through-a specific protease called MEL-asso ciated protease-2. We have used flow cytometry to study both the binding of MBL to microorganisms and the subsequent activation of complement. For sel ected Gram-negative organisms, such as Salmonella and Neisseria, we have ex amined the relative roles of lipopolysaccharide (LPS) structure and capsule in determining binding and conclude that the LPS is of major importance. O ur results from studies with several clinically relevant organisms also sho w that MBL binding detected by flow cytometry leads to measurable activatio n of purified C4, suggesting that the. bound lectin is capable-of initiatin g opsonophagocytosis and/or bacterial lysis. There is an increasing literat ure suggesting that MBL deficiency, which mainly results from three relativ ely common single point mutations in exon I of the gene, predisposes both t o infection by extracellular pathogens and to autoimmune disease. In additi on, the protein also modulates disease severity, at least in part through a complex, dose-dependent influence on cytokine production. The mechanisms a nd signalling pathways involved in such processes remain to be elucidated.