Antibodies Directed againstO‐Acetylated Sialoglycoconjugates Accelerate Complement Activation inLeishmania donovaniPromastigotes

Bandyopadhyay, Sumi; Chatterjee, Mitali; Das, Tanusree; Bandyopadhyay, Suman; Sundar, Shyam; Mandal, Chitra

doi:10.1086/425519

Cited by 24 publications

(20 citation statements)

References 32 publications

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“…When serum from normal (NHS) and malaria patients (MS) were used as sources of complements separately, comparable C3-deposition in presence of CRP Mal was observed on RBC Mal being 92±2% and 90±6% respectively. This suggested undisturbed complement components in diseased state, as observed by our previous reports in other diseases [46][47]. Similar result was observed in presence of CRP-depleted patient's sera (91±5%).…”

Section: Crp Triggered Complement-cascade With Concomitant C3-depositionsupporting

confidence: 90%

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Unraveling the C-reactive Protein Complement-Cascade in Destruction of Red Blood Cells: Potential Pathological Implications in Plasmodium Falciparum Malaria

Ansar

Habib²,

Roy³

et al. 2009

Cell Physiol Biochem

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Background: Deficiencies of the complementregulatory proteins on RBC (RBC Mal ) of patients with Plasmodium falciparum were reported. Here, we sought to determine the role of affinity-purified Creactive 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, flowcytometry 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. Flowcytometry, ELISA, Western blotting and Scatchard analysis monitored the status of complementregulatory 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 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 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.

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Section: Crp Triggered Complement-cascade With Concomitant C3-depositionsupporting

confidence: 90%

“…However, CRP is unable to trigger the alternate pathway [46]. As EGTA is known to trigger alternate pathway, C3-deposition through this pathways was measured, being only 23 ± 3%.…”

Section: Crp Triggered Complement-cascade With Concomitant C3-depositionmentioning

confidence: 92%

Unraveling the C-reactive Protein Complement-Cascade in Destruction of Red Blood Cells: Potential Pathological Implications in Plasmodium Falciparum Malaria

Ansar

Habib²,

Roy³

et al. 2009

Cell Physiol Biochem

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“…Previous studies by our group, using the preferential binding specificity of achatinin-H, have shown the expression on the cell surface of promastigotes of two specific 9-O-AcSGPs with molecular masses of 123 and 109 kDa (8,27). Concomitantly, enhanced anti-9-O-AcSGP-specific antibody responses against these parasite-specific sialoglycoproteins have been witnessed as a part of the host defense mechanism (5,6,10,39). Furthermore, these antibodies, as reported earlier, are leishmanicidal in activity; that is, they are capable of triggering the classical complement pathway, thereby causing Leishmania cell death (5).…”

Section: Discussionmentioning

confidence: 91%

“…Concomitantly, enhanced anti-9-O-AcSGP-specific antibody responses against these parasite-specific sialoglycoproteins have been witnessed as a part of the host defense mechanism (5,6,10,39). Furthermore, these antibodies, as reported earlier, are leishmanicidal in activity; that is, they are capable of triggering the classical complement pathway, thereby causing Leishmania cell death (5). Alternatively, several other 9-OAcSGPs have been documented on immune cells (65, 56, and 19 kDa) and erythrocytes (112, 107, 103, 57, 51, and 48 kDa) of VL patients (4,11,22).…”

Section: Discussionmentioning

confidence: 99%

9-O-Acetylated Sialoglycoproteins Are Important Immunomodulators in Indian Visceral Leishmaniasis

Ghoshal

Mukhopadhyay

Saha

et al. 2009

Clin Vaccine Immunol

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“…To analyze the kinetics of sialoglycoproteins binding by Achatinin-H, the lectin was iodinated with 125 I (Amersham Pharmacia Biotech, Sweden) by the chloramine T method [18] yielding a specific activity of 1.5×10 6 cpm/μg. For measuring the binding to cells, PBMC (2×10 6 /150 μL per tube) from five patients were suspended in 10 μL RPMI-1640 medium containing CaCl 2 (0.3 M) and bovine serum albumin (BSA, 0.2%), pH 7.2 (reaction buffer).…”

Section: Binding Assaysmentioning

confidence: 99%

Detection and characterization of a sialoglycosylated bacterial ABC-type phosphate transporter protein from patients with visceral leishmaniasis

et al. 2009

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We report the discovery and characterization of a glycosylated bacterial ABC-type phosphate transporter isolated from the peripheral blood mononuclear cell (PBMC) fraction of patients with visceral leishmaniasis (VL). Three disease-associated 9-O-acetylated sialoglycoproteins (9-O-AcSGPs) of 19, 56 and 65 kDa, respectively, had been identified and their purity, apparent mass and pI established by SDS-PAGE and isoelectric focusing. Western blot analyses showed that the 9-O-acetylated sialic acid is linked via alpha2-->6 linkage to a subterminal N-acetylgalactosamine. For the 56 kDa protein, N- as well as O-glycosylations were demonstrated by specific glycosidase treatment and found to account for more than 9 kDa of the protein mass. The presence of sialic acids was further confirmed through thin layer chromatography, fluorimetric HPLC and electrospray ionization-mass spectrometry. The protein was identified by mass spectrometry and de novo sequencing of five tryptic fragments as a periplasmic ABC-type phosphate transporter of Pseudomonas aeruginosa. The amino acid sequences of the assigned peptides had 83-100% identity with the NCBI entry for a Pseudomonas transporter protein. Based on the recently reported X-ray structure of a human phosphate-binding protein, we predicted a 3D structural model for the 56 kDa protein using homology and threading methods. The most probable N- and O-glycosylation sites were identified by combinations of sequence motif-searching bioinformatics tools, solvent accessibility calculations, structural environment analyses and mass spectrometric data. This is the first reported glycosylation as well as sialylation of the periplasmic component of an ABC-type phosphate transporter protein and of one of few identified bacterial glycoproteins.

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Antibodies Directed againstO‐Acetylated Sialoglycoconjugates Accelerate Complement Activation inLeishmania donovaniPromastigotes

Abstract: Anti-O-AcSGs were identified as an important source of CP activation under normal physiological conditions, suggesting that they play a role in conferring host protection against parasite infection.

Cited by 24 publications

References 32 publications

Unraveling the C-reactive Protein Complement-Cascade in Destruction of Red Blood Cells: Potential Pathological Implications in <i>Plasmodium Falciparum</i> Malaria

Unraveling the C-reactive Protein Complement-Cascade in Destruction of Red Blood Cells: Potential Pathological Implications in <i>Plasmodium Falciparum</i> Malaria

9-O-Acetylated Sialoglycoproteins Are Important Immunomodulators in Indian Visceral Leishmaniasis

Detection and characterization of a sialoglycosylated bacterial ABC-type phosphate transporter protein from patients with visceral leishmaniasis

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