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 2M). Binding between these three molecules was in an ascending order of MBP, MASP and alpha 2M, in that alpha 2M bound directly to MASP, possibly through covalent bonds, whereas the binding between MBP and MASP was reversible and Ca(2+)-dependent. Since it was found that alpha 2M can inhibit complement activation by MASP and that MASP in the complex lacks esterolytic activity, it is conceivable that alpha 2M plays a regulatory role in MBP-derived complement activation via a mechanism involving MASP (the lectin pathway).
Terai
I
I
Department of Laboratory Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Kobayashi
K
K
Matsushita
M
M
Fujita
T
T
Matsuno
K
K
D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D046911:Macromolecular Substances; D037241:Mannose-Binding Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000378:metabolism* / Q000494:pharmacology
D002352:Carrier Proteins; D046911:Macromolecular Substances; D037241:Mannose-Binding Lectins; D015842:Serine Proteinase Inhibitors; D000511:alpha-Macroglobulins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases; D002118:Calcium