Mannose-Binding Lectin Has Diagnostic Role

Researchers have found that elevated levels of mannose-binding lectin (MBL) in the blood are associated with a lower risk of heart attack, particularly among diabetics.

Mannose-binding lectin (MBL), also named mannose- or mannan-binding protein, is an important factor in the innate immune system. MBL belongs to the class of collectins in the C-type lectin superfamily, whose function appears to be pattern recognition in the first line of defense in the pre-immune host. MBL recognizes carbohydrate patterns, found on the surface of a large number of pathogen microorganisms, including bacteria, viruses, protozoa, and fungi. Binding of MBL to a microorganism results in activation of the classical complement route, long before specific antibodies are formed.


MBL has an oligomeric structure (400-700 kDa), built of subunits that contain three identical peptide chains of 32 kDa each. Although MBL can form different oligomers, there are indications that dimers and trimers are not biologically active and at least a tetramer form is needed for activation of complement. The peptide chains consist of a collagen-like part and a lectin part. The lectin part binds via carbohydrate recognition domains (CRDs) at different sugar groups such as mannose, maltose, N-acetylglucosamine, N-acetylgalactosamine, fucose, and glucose.


In the circulation MBL forms a functional complex with MASPs (MBL-associated serine protease) 1, 2 and 3, which becomes enzymatically active, after binding with a microorganism. MASP-2 is identical to C1-esterase in the classical complement route and is able to split C4 and C2, whereupon C4b2a is formed. C4b2a functions as C3-convertase and splits C3, whereupon C3b is formed that causes opsonization of the microbe.


There are indications that MBL binds directly to collectin receptors on the surface of phagocytes, and it has been suggested that MBL binds to the C1q receptor on neutrophil granulocytes, monocytes, and macrophages. Binding to effector cells may stimulate the production of pro-inflammatory cytokines.


Investigators at Landspitali-University Hospital (Reykjavik, Iceland) analyzed levels of MBL in subgroups of the population-based Reykjavik study, a cohort of 19,381 participants recruited from 1967. They reported in the January 3, 2005, issue of the Journal of Experimental Medicine that MBL levels were very stable over time, and that high MBL levels were associated with greatly decreased heart-attack risk in diabetic or hypercholesterolemic individuals.

The authors suggested that their findings indicated that high MBL levels could predict decreased likelihood of a heart attack, particularly in diabetics, and were consistent with the possibility that MBL may promote clearance of atherogenic agents.



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Landspitali-University Hospital