Hypochlorite-induced structural modifications enhance the chaperone activity of human α2-macroglobulin

Hypochlorite is a powerful oxidant that is generated within the body by activated innate immune cells. When hypochlorite is produced, the host organism sustains collateral damage, particularly to proteins, and the accumulation of damaged (misfolded) proteins is a hallmark of inflammatory processes (e.g., in Alzheimer's disease, atherosclerosis, and arthritis). In the present study, we show that the chaperone activity of human α₂-macroglobulin, a highly abundant secreted protein, is dramatically increased by hypochlorite-induced structural modifications. The data support the conclusion that α₂-macroglobulin is a unique component of the innate immune system that is posttranslationally regulated by hypochlorite to facilitate the clearance of potentially pathogenic misfolded proteins.