Heterogeneity of MBL-MASP complexes.

ABSTRACT

In order to study aspects of the stoichiometry and composition of human MBL-MASP complexes in the population, MBL-MASP complexes were bound from sera of 152 healthy individuals onto mannan-coated microtitre plates. Bound mannan-binding lectin (MBL) was measured by ELISA, and the enzyme activities of MBL-bound MASP-1 and MASP-2 were measured by an amidolytic assay and a C4 fixation assay, respectively. MASP-1 activity correlated with MBL concentration, as did MASP-2 activity (in both cases p<0.0001). This is expected since MASP-1 and MASP-2 are bound to the mannan via MBL. However, when MASP activities were normalised to MBL concentration (i.e. MASP-1 activity/[MBL], MASP-2 activity/[MBL]) MASP-1 activity was inversely correlated with MASP-2. This means on average that high MASP-1 correlates with low MASP-2 and vice-versa, and confirms the hypothesis that native MBL-MASP complexes on average do not have fixed MBL-(MASP-1)-(MASP-2) stoichiometry. The findings are consistent with separate populations of MBL-MASP-1 complexes and MBL-MASP-2 complexes, the concentrations of which show wide inter-individual variation.