Discrete MBL-MASP complexes show wide inter-individual variability in concentration: data from UK vs Armenian
K R Mayilyan1, J S Presanis, J N Arnold
1MRC Immunochemistry Unit, Department of Biochemistry, Oxford University, Oxford, UK.
Abstract:
Mannan-binding lectin (MBL) circulates in plasma in complex with MBL-associated serine proteases (MASP) -1, -2 and -3 and a smaller component, MAp19. When MBL binds to the surface of foreign material (microorganisms), MASP-1, -2, -3 are activated. MASP-2 then activates the complement system. MASP-1 and -3 may activate other (unidentified) systems. MBL levels, MBL-bound MASP-1 and MBL-bound MASP-2 activities have been evaluated in healthy individuals from UK and Armenian populations. MBL-bound MASP-2 activity declines in aging (P<0.04). MBL correlates with smoking (P<0.02). There were significant differences between the two populations in MBL-bound MASP-1 activity and in MBL, but no difference in MBL-bound MASP-2 activity. When MASP activities were normalised to MBL (i.e. MASP-1 activity/MBL, MASP-2 activity/MBL), normalised MASP-2 activity in UK individuals was more than 2 fold higher than in Armenians. The difference in normalised MASP-2 activity level between these two Caucasoid populations, suggests that concentration of the MBL-(MASP-2) complex, and therefore the function of activating complement, depends not only on the quantity of MBL in serum and its oligomeric state, but also on the quantity of MASP-2 in serum. It is likely that in individuals with high MBL concentration there is excess free MBL not occupied by MASPs, particularly not by MASP-2.
Insights
Mannan-binding lectin (MBL) and its associated serine proteases (MASP) play roles in the immune system. This study found differences in MBL-MASP complex activity between UK and Armenian populations, suggesting MASP-2 levels influence complement activation.
Area of Science:
- Immunology
- Complement System
- Protease Activity
Background:
- Mannan-binding lectin (MBL) circulates with MBL-associated serine proteases (MASPs) and activates the complement system upon microbial binding.
- MASP-2 activation is crucial for the complement cascade, while MASP-1 and MASP-3 roles are less defined.
- MBL levels and MASP activities can be influenced by factors like aging and smoking.
Purpose of the Study:
- To evaluate MBL levels and MBL-bound MASP-1 and MASP-2 activities in healthy UK and Armenian populations.
- To investigate the relationship between MBL, MASP activities, and demographic factors like age and smoking.
- To compare the normalized MASP activities between the two distinct populations.
Main Methods:
- Quantification of MBL levels in plasma.
- Assay of MBL-bound MASP-1 and MASP-2 activities.
- Statistical analysis to compare MBL and MASP parameters between UK and Armenian populations.
- Normalization of MASP activities to MBL levels to assess complex concentration.
Main Results:
- MBL-bound MASP-2 activity showed a decline with aging.
- MBL levels correlated positively with smoking.
- Significant differences were observed in MBL and MBL-bound MASP-1 activity between populations, but not in MBL-bound MASP-2 activity.
- Normalized MASP-2 activity was over twofold higher in UK individuals compared to Armenians.
- High MBL concentrations may be associated with excess free MBL not bound to MASPs.
Conclusions:
- Complement activation efficiency, mediated by the MBL-MASP-2 complex, is influenced by both MBL quantity and MASP-2 concentration.
- Differences in normalized MASP-2 activity between populations suggest variations in MASP-2 serum levels.
- The findings highlight the complex interplay between MBL, MASPs, and complement function, with potential implications for immune response variability.
