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Sialoglycosylation of RBC in Visceral Leishmaniasis Leads to Enhanced Oxidative Stress, Calpain-Induced Fragmentation of Spectrin and Hemolysis

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Title Sialoglycosylation of RBC in Visceral Leishmaniasis Leads to Enhanced Oxidative Stress, Calpain-Induced Fragmentation of Spectrin and Hemolysis
 
Creator Samanta, Sajal
Ghoshal, Angana
Bhattacharya, Kaushik
Saha, Bibhuti
Walden, Peter
Mandal, Chitra
 
Subject Infectious Diseases and Immunology
 
Description Visceral leishmaniasis (VL) caused by the intracellular parasite Leishmania donovani accounts for an estimated 12 million
cases of human infection. It is almost always associated with anemia, which severely complicates the disease course.
However, the pathological processes leading to anemia in VL have thus far not been adequately characterized to date. In
studying the glycosylation patterns of peripheral blood cells we found that the red blood cells (RBC) of VL patients (RBCVL)
express eight 9-O-acetylated sialoglycoproteins (9-O-AcSGPs) that are not detected in the RBC of healthy individuals (RBCN).
At the same time, the patients had high titers of anti-9-O-AcSGP IgG antibodies in their sera. These two conditions appear to
be linked and related to the anemic state of the patients, as exposure of RBCVL but not RBCN to anti-9-O-AcSGPs antibodies
purified from patient sera triggered a series of responses. These included calcium influx via the P/Q-type but not L-type
channels, activation of calpain I, proteolysis of spectrin, enhanced oxidative stress, lipid peroxidation, externalization of
phosphatidyl serine with enhanced erythrophagocytosis, enhanced membrane fragility and, finally, hemolysis. Taken
together, this study suggests that the enhanced hemolysis is linked to an impairment of membrane integrity in RBCVL which
is mediated by ligand-specific interaction of surface 9-O-AcSGPs. This affords a potential explanation for the structural and
functional features of RBCVL which are involved in the hemolysis related to the anemia which develops in VL patients.
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1728/1/PLOS_ONE___7_(7_)___Article_Number_e42361;2012[66].pdf
Samanta, Sajal and Ghoshal, Angana and Bhattacharya, Kaushik and Saha, Bibhuti and Walden, Peter and Mandal, Chitra (2012) Sialoglycosylation of RBC in Visceral Leishmaniasis Leads to Enhanced Oxidative Stress, Calpain-Induced Fragmentation of Spectrin and Hemolysis. PLoS ONE, 7 (7). e42361.
 
Relation http://dx.doi.org/10.1371/journal.pone.0042361
http://www.eprints.iicb.res.in/1728/