ALPHA(2)-MACROGLOBULIN BINDS TO AND INHIBITS MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE-PROTEASE

We determined the presence in human serum of a complex consisting of mannose-binding protein (MBP), MBP-associated serine protease (MASP), which is a C1s-like protein with complement activation activity, and alpha(2)-macroglobulin (alpha(2)M). Binding between these three molecules was in an ascending order of MBP, MASP and alpha(2)M, in that alpha(2)M bound directly to MASP, possibly through covalent bonds, whereas the binding between MBP and MASP was reversible and Ca2+-dependent. Since it was found that alpha(2)M can inhibit complement activation by MASP and that MASP in the complex lacks esterolytic activity, it is conceivable that alpha(2)M plays a regulatory role in MBP-derived complement activation via a mechanism involving MASP (the lectin pathway).