Disease-associated glycosylated molecular variants of human C-reactive protein activate complement-mediated hemolysis of erythrocytes in tuberculosis and Indian visceral leishmaniasis
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Disease-associated glycosylated molecular variants
of human C-reactive protein activate complement-mediated
hemolysis of erythrocytes in tuberculosis and Indian
visceral leishmaniasis
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| Creator |
Ansar, Waliza
Mukhopadhyay , Sumi Hasan Habib, S K Basu, Shyamasree Saha, Bibhuti Sen, Asish Kumar Mandal, Chhabinath Mandal, Chitra |
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| Subject |
Infectious Diseases and Immunology
Structural Biology & Bioinformatics |
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| Description |
Human C-reactive protein (CRP), as a mediator
of innate immunity, removed damaged cells by activating
the classical complement pathway. Previous studies have
successfully demonstrated that CRPs are differentially induced
as glycosylated molecular variants in certain pathological
conditions. Affinity-purified CRPs from two most
prevalent diseases in India viz. tuberculosis (TB) and
visceral leishmaniasis (VL) have differential glycosylation
in their sugar composition and linkages. As anemia is a
common manifestation in TB and VL, we assessed the
contributory role of glycosylated CRPs to influence hemolysis
via CRP-complement-pathway as compared to
healthy control subjects. Accordingly, the specific binding
of glycosylated CRPs with erythrocytes was established by
flow-cytometry and ELISA. Significantly, deglycosylated
CRPs showed a 7–8-fold reduced binding with erythrocytes
confirming the role of glycosylated moieties. Scatchard
analysis revealed striking differences in the apparent binding constants (104–105M−1) and number of binding
sites (106–107sites/erythrocyte) for CRP on patients’ erythrocytes
as compared to normal. Western blotting along with
immunoprecipitation analysis revealed the presence of
distinct molecular determinants on TB and VL erythrocytes
specific to disease-associated CRP. Increased fragility, hydrophobicity
and decreased rigidity of diseased-erythrocytes
upon binding with glycosylated CRP suggested membrane
damage. Finally, the erythrocyte-CRP binding was shown to
activate the CRP-complement-cascade causing hemolysis,
even at physiological concentration of CRP (10μg/ml).
Thus, it may be postulated that CRP have a protective role
towards the clearance of damaged-erythrocytes in these two
diseases
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| Publisher |
Kluwer
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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/168/1/GLYCOCONJUGATE_JOURNAL%2C26(9)%2C1151%2D1169%2C2009[6].pdf
Ansar, Waliza and Mukhopadhyay , Sumi and Hasan Habib, S K and Basu, Shyamasree and Saha, Bibhuti and Sen, Asish Kumar and Mandal, Chhabinath and Mandal, Chitra (2009) Disease-associated glycosylated molecular variants of human C-reactive protein activate complement-mediated hemolysis of erythrocytes in tuberculosis and Indian visceral leishmaniasis. Glycoconjugate Journal, 26. pp. 1151-1169. |
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| Relation |
http://dx.doi.org/10.1007/s10719-009-9236-y
http://www.eprints.iicb.res.in/168/ |
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