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 m annose-binding protein (MBP), MBP-associated serine protease (MASP), w hich is a C1s-like protein with complement activation activity, and al pha(2)-macroglobulin (alpha(2)M). Binding between these three molecule s 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 t he binding between MBP and MASP was reversible and Ca2+-dependent. Sin ce it was found that alpha(2)M can inhibit complement activation by MA SP and that MASP in the complex lacks esterolytic activity, it is conc eivable that alpha(2)M plays a regulatory role in MBP-derived compleme nt activation via a mechanism involving MASP (the lectin pathway).