Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19

Mannan-binding lectin (MEL) and Clq activate the complement cascade via attached serine proteases, The proteases Clr and Cls were initially discovered in a complex with Clq, whereas the MEL-associated serine proteases 1 and 2 (MASP-1 and -2) were discovered in a complex with MEL. There is controversy as to whether MBL can utilize Clr and Cls or, inversely, whether Clq can utilize MASP-1 and 2, Serum deficient in Clr produced no complement activation in IgG-coated microwells, whereas activation was seen in mannan-coated microwells, In serum, Clr and Cls were found to be associated only with Clq, whereas MASP-1, MASP-2, and a third protein, MAp19 (19-kDa MEL-associated protein), were found to be associated only with MEL. The bulk of MASP-1 and MAp19 was found in association with each other and was not bound to MEL or MASP-2, The interactions of MASP-1, MASP-2, and MAp19 with MEL differ from those of Clr and Cls with Clq in that both high salt concentrations and calcium chelation (EDTA) are required to fully dissociate the MASPs or MAp19 from MEL, In the presence of calcium, most of the MASP-1, MASP-2, and MAp19 emerged on gel-permeation chromatography as large complexes that were not associated with MEL, whereas in the presence of EDTA most of these components formed smaller complexes. Over 95% of the total MASPs and MAp19 found in serum are not complexed with MBL.