Acute phase proteins are major clients for the chaperone action of α2-macroglobulin in human plasma

Extracellular protein misfolding is implicated in many age-related diseases including Alzheimer's disease, macular degeneration and arthritis. In this study, putative endogenous clients for the chaperone activity of alpha(2)-macroglobulin (alpha M-2) were identified after human plasma was subjected to physiologically relevant sheer stress at 37 A degrees C for 10 days. Western blot analysis showed that four major acute phase proteins: ceruloplasmin, fibrinogen, alpha(1)-acid glycoprotein and complement component 3, preferentially co-purified with alpha M-2 after plasma was stressed. Furthermore, the formation of complexes between alpha M-2 and these putative chaperone clients, detected by sandwich ELISA, was shown to be enhanced in response to stress. These results support the hypothesis that alpha M-2 plays an important role in extracellular proteostasis by sequestering misfolded proteins and targeting them for disposal, particularly during acute phase reactions.