Unraveling the C-reactive Protein Complement- Cascade in Destruction of Red Blood Cells: Potential Pathological Implications in Plasmodium Falciparum Malaria
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Unraveling the C-reactive Protein Complement-
Cascade in Destruction of Red Blood Cells:
Potential Pathological Implications in Plasmodium
Falciparum Malaria
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| Creator |
Ansar, Waliza
Habib, SK Hasan Roy, Samir Mandal, Chhabinath Mandal, Chitra |
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| Subject |
Infectious Diseases and Immunology
Structural Biology & Bioinformatics |
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| Description |
Background: Deficiencies of the complementregulatory
proteins on RBC (RBCMal) of patients with
Plasmodium falciparum were reported. Here, we
sought to determine the role of affinity-purified Creactive
protein from patients (CRPMal), in modulating
the complement-regulatory proteins and downstream
effect on complement-cascade. Methods: CRPMal was
characterized by analytical ultracentrifuge and
electrophoretic analysis. Surface plasmon resonance,
Western blotting, co-immuno-precipitation, flowcytometry
and ELISA determined the binding of CRPMal
with RBCMal. Modifications of membranes for RBCMal-
CRPMal binding were explored by scanning electron
microscopy, osmotic and turbulence fragility,
hydrophobicity and oxyhemoglobin release. Flowcytometry,
ELISA, Western blotting and Scatchard
analysis monitored the status of complementregulatory
proteins on RBCMal. Complement-activation
via CRPMal was quantified by C3-deposition and
hemolysis. Results: CRPMal binds specifically to RBCMal
through distinct molecules. Such binding altered the normal discoid-shape of RBCMal with increased
membrane fluidity and hydrophobicity. In the presence
of CRP, RBCMal showed reduced complementregulatory
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 CRPMal causing
decreased complement-regulatory proteins, possibly
providing a new mechanism of complement-fueled
RBCMal destruction refractory to erythrophagocytosis
and may account for pathogenesis of anemia.
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| Date |
2009
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/139/1/CELLULAR_PHYSIOLOGY_AND_BIOCHEMISTRY%2C_23(1%2D3)%2C175%2D190%2C_2009[132].pdf
Ansar, Waliza and Habib, SK Hasan and Roy, Samir and Mandal, Chhabinath and Mandal, Chitra (2009) Unraveling the C-reactive Protein Complement- Cascade in Destruction of Red Blood Cells: Potential Pathological Implications in Plasmodium Falciparum Malaria. Cell Physiol Biochem, 23 (1-3). pp. 175-190. |
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| Relation |
http://dx.doi.org/10.1159/000204106
http://www.eprints.iicb.res.in/139/ |
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