Unraveling the C-reactive protein complement-cascade in destruction of red blood cells: potential pathological implications in Plasmodium falciparum malaria

Cell Physiol Biochem. 2009;23(1-3):175-90. doi: 10.1159/000204106. Epub 2009 Feb 18.


Background: Deficiencies of the complement-regulatory proteins on RBC (RBC(Mal)) of patients with Plasmodium falciparum were reported. Here, we sought to determine the role of affinity-purified C-reactive protein from patients (CRP(Mal)), in modulating the complement-regulatory proteins and downstream effect on complement-cascade.

Methods: CRP(Mal) was characterized by analytical ultracentrifuge and electrophoretic analysis. Surface plasmon resonance, Western blotting, co-immuno-precipitation, flow-cytometry and ELISA determined the binding of CRP(Mal) with RBC(Mal). Modifications of membranes for RBC(Mal)-CRP(Mal) binding were explored by scanning electron microscopy, osmotic and turbulence fragility, hydrophobicity and oxyhemoglobin release. Flow-cytometry, ELISA, Western blotting and Scatchard analysis monitored the status of complement-regulatory proteins on RBC(Mal). Complement-activation via CRP(Mal) was quantified by C3-deposition and hemolysis.

Results: CRP(Mal) binds specifically to RBC(Mal) through distinct molecules. Such binding altered the normal discoid-shape of RBC(Mal) with increased membrane fluidity and hydrophobicity. In the presence of CRP, RBC(Mal) showed reduced complement-regulatory proteins (CR1 or CD35, CD55 and CD59) with decreased affinity. These changes caused enhanced C3-deposition and complement-mediated hemolysis.

Conclusion: Taken together, we have established the contributory effect of CRP(Mal) causing decreased complement-regulatory proteins, possibly providing a new mechanism of complement-fueled RBC(Mal) destruction refractory to erythrophagocytosis and may account for pathogenesis of anemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Binding Sites / physiology
  • Blotting, Western
  • C-Reactive Protein / metabolism*
  • CD55 Antigens / metabolism
  • CD59 Antigens / metabolism
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Erythrocytes / metabolism*
  • Erythrocytes / parasitology*
  • Erythrocytes / ultrastructure
  • Flow Cytometry
  • Humans
  • Microscopy, Electron, Scanning
  • Middle Aged
  • Plasmodium falciparum / pathogenicity*
  • Plasmodium falciparum / physiology
  • Protein Binding / physiology
  • Receptors, Complement 3b / metabolism
  • Surface Plasmon Resonance
  • Young Adult


  • CD55 Antigens
  • CD59 Antigens
  • CR1 protein, human
  • Receptors, Complement 3b
  • C-Reactive Protein