Mannan-binding lectin: clinical significance and applications.
Mannan-binding lectin (MBL) is a collectin (protein with both collagen-like and C-type lectin domains) synthesised in the liver and secreted into the bloodstream. Its plasma concentration is for the most part genetically determined by a series of allelic dimorphisms located both in the structural gene and in the promoter region. Genotypes made up of combinations of seven haplotypes are mainly responsible for a 1000-fold concentration variation found in human beings. MBL is a pattern recognition molecule able to bind repeating sugar arrays on many microbial surfaces, and can activate complement via associated serine proteases. A poorly defined proportion (roughly 10%) of the population with the lowest MBL concentrations is thought to be MBL insufficient and more vulnerable to a variety of infectious and noninfectious disorders. The evidence that MBL makes an important contribution to innate immunity, by increasing susceptibility to disease and/or affecting the course of disease, is discussed in detail. Preliminary results from MBL replacement therapy are encouraging, and extension of this approach to large-scale randomised clinical trials would provide solid evidence concerning the physiological significance of this protein.
Kilpatrick
David C
DC
Scottish National Blood Transfusion Service, National Science Laboratory, Ellen's Glen Road, EH17 7QT, Scotland, Edinburgh, UK.
D000483:Alleles; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000503:physiopathology; D001424:Bacterial Infections / Q000503:physiopathology; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D037222:Collectins; D003167:Complement Activation; D003550:Cystic Fibrosis / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D016867:Immunocompromised Host; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology; D009181:Mycoses / Q000503:physiopathology; D014777:Virus Diseases / Q000503:physiopathology
D002352:Carrier Proteins; D037222:Collectins