Publication Details

Wyatt, A. R. & Wilson, M. R. (2013). Acute phase proteins are major clients for the chaperone action of α2-macroglobulin in human plasma. Cell Stress and Chaperones, 18 (2), 161-170.


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 α2-macroglobulin (α2M) were identified after human plasma was subjected to physiologically relevant sheer stress at 37 °C for 10 days. Western blot analysis showed that four major acute phase proteins: ceruloplasmin, fibrinogen, α1-acid glycoprotein and complement component 3, preferentially co-purified with α2M after plasma was stressed. Furthermore, the formation of complexes between α2M and these putative chaperone clients, detected by sandwich ELISA, was shown to be enhanced in response to stress. These results support the hypothesis that α2M plays an important role in extracellular proteostasis by sequestering misfolded proteins and targeting them for disposal, particularly during acute phase reactions.



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