Oxidation of C-reactive protein by hypochlorous acid leads to the formation of potent platelet activator

Int J Biol Macromol. 2018 Feb;107(Pt B):2701-2714. doi: 10.1016/j.ijbiomac.2017.10.159. Epub 2017 Oct 28.


We examined the structural and functional consequences of oxidative modification of C-reactive protein (CRP) by hypochlorous acid (HOCl), which can be generated in vivo via the myeloperoxidase/H2O2/Cl- system. HOCl exposure resulted in the oxidation and chlorination of CRP amino acid residues, leading to protein unfolding, greater surface hydrophobicity and the formation of aggregates. After treatment of isolated platelets with 50μg/ml HOCl-CRP, the modified CRP significantly stimulated platelet activation (over 10-fold increase in the fraction of CD62-positive platelets compared to controls, P<0.008), enhanced deposition of platelets onto immobilized fibrinogen (two-fold rise in platelet adhesion compared to controls, P<0.0001), and induced platelet aggregation by up to 79.5%. The ability of HOCl-CRP to interact with several platelet receptors (TLR-4, GPIIbIIIa) and plasma proteins (C1q, IgG) strongly indicates that HOCl-modification leads to structural changes of CRP resulting in the formation of new ligand binding sites, which is characteristic of the monomeric form of CRP exerting pro-inflammatory effects on a variety of cells. Overall, the oxidation of native CRP by HOCl seems to represent an alternative mechanism of CRP modification, by which CRP reveals its pro-inflammatory and pro-thrombotic properties, and as such, it might be of causal relevance in the pathogenesis of atherosclerosis.

Keywords: Atherosclerosis; C-reactive protein; Hypochlorous acid; Inflammation; Oxidation; Platelet.

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adsorption
  • Adult
  • Amino Acid Sequence
  • Benzothiazoles
  • C-Reactive Protein / chemistry
  • C-Reactive Protein / metabolism*
  • Collagen / pharmacology
  • Female
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Hypochlorous Acid / pharmacology*
  • Kinetics
  • Ligands
  • Male
  • Oxidation-Reduction
  • P-Selectin / metabolism
  • Phosphorylation / drug effects
  • Platelet Activation / drug effects*
  • Platelet Adhesiveness / drug effects
  • Polystyrenes / chemistry
  • Protein Aggregates
  • Spectrometry, Fluorescence
  • Surface Plasmon Resonance
  • Surface Properties
  • Tandem Mass Spectrometry
  • Thiazoles / metabolism


  • Benzothiazoles
  • Ligands
  • P-Selectin
  • Polystyrenes
  • Protein Aggregates
  • Thiazoles
  • thioflavin T
  • Adenosine Diphosphate
  • Hypochlorous Acid
  • Collagen
  • C-Reactive Protein