Functional transformation of C-reactive protein by hydrogen peroxide [Immunology]

C-reactive protein (CRP) is present at sites of inflammation including amyloid plaques, atherosclerotic lesions and arthritic joints. CRP, in its native pentameric structural conformation, binds to cells and molecules which have exposed phosphocholine (PCh) groups. CRP, in its non-native pentameric structural conformation, binds to a variety of deposited, denatured and aggregated proteins, in addition to binding to PCh-containing substances. In this study, we investigated the effects of hydrogen peroxide (H2O2), a prototypical reactive oxygen species and which is also present at sites of inflammation, on the ligand recognition function of CRP. Controlled H2O2-treatment of native CRP did not monomerize CRP and did not affect the PCh-binding activity of CRP. In solid-phase ELISA-based ligand binding assays, purified pentameric H2O2-treated CRP bound to a number of immobilized proteins including oxidized LDL, IgG, amyloid beta peptide 1-42, C4b-binding protein and factor H, in a CRP-concentration and ligand-concentration dependent manner. Using oxidized LDL as a representative protein-ligand for H2O2-treated CRP, we found that the binding occurred in a Ca2+-independent manner and did not involve the PCh-binding site of CRP. We conclude that H2O2 is a biological modifier of the structure and ligand recognition function of CRP. Overall, the data suggest that the ligand recognition function of CRP is dependent on the presence of an inflammatory microenvironment. We hypothesize that one of the functions of CRP at sites of inflammation is to sense the inflammatory microenvironment, change its own structure in response but remain pentameric, and then bind to pathogenic proteins deposited at those sites.

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