PMID- 15529267 OWN - NLM STAT- MEDLINE DCOM- 20041230 LR - 20061115 IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 190 IP - 11 DP - 2004 Dec 1 TI - Antibodies directed against O-acetylated sialoglycoconjugates accelerate complement activation in Leishmania donovani promastigotes. PG - 2010-9 AB - BACKGROUND: An enhanced presence of 9-O-acetylated sialoglycoconjugates (9-O-AcSGs) triggers the alternate pathway (AP) in Indian visceral leishmaniasis (VL). Antibodies directed against these epitopes are present in high titers. The biological relevance of these antibodies, with regard to activation of the classical pathway (CP), was investigated. METHODS: Complement activators were affinity purified, complement activation via the CP, AP, and lectin-mediated complement pathway was measured by use of an anti-C3 radio-binding assay, and the number of C3 molecules was quantitated by Scatchard analysis. Cell death induced via the complement pathways was measured by use of MTT (tetrazolium salt 3- [4, 5-dimethylthiazol-2-yl] -2, 5-diphenyltetrazolium bromide) assay, and uptake of propidium iodide (PI) was measured by flow cytometry. RESULTS: Anti-O-AcSGs from both healthy donors and patients with VL elicited C3 deposition as early as 3 min, which triggered parasite lysis, as demonstrated by use of MTT assay and corroborated by the high rate of uptake of PI. Analysis of complement activation by mannan-binding lectin and C-reactive protein demonstrated their negligible contribution during the 3-min time frame. CONCLUSIONS: 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. FAU - Bandyopadhyay, Sumi AU - Bandyopadhyay S AD - Immunobiology Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700-032, India. FAU - Chatterjee, Mitali AU - Chatterjee M FAU - Das, Tanusree AU - Das T FAU - Bandyopadhyay, Suman AU - Bandyopadhyay S FAU - Sundar, Shyam AU - Sundar S FAU - Mandal, Chitra AU - Mandal C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20041103 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Antibodies, Protozoan) RN - 0 (Complement C3) RN - 0 (Glycoconjugates) SB - IM MH - Animals MH - Antibodies, Protozoan/isolation & purification/*pharmacology MH - Complement Activation/*drug effects MH - Complement C3/analysis/*immunology MH - Complement Pathway, Alternative/drug effects MH - Complement Pathway, Classical/drug effects MH - Dose-Response Relationship, Immunologic MH - Glycoconjugates/*immunology MH - Humans MH - Leishmania donovani/drug effects/*immunology MH - Leishmaniasis, Visceral/blood/*immunology MH - Time Factors EDAT- 2004/11/06 09:00 MHDA- 2004/12/31 09:00 CRDT- 2004/11/06 09:00 PHST- 2004/03/17 00:00 [received] PHST- 2004/06/14 00:00 [accepted] PHST- 2004/11/06 09:00 [pubmed] PHST- 2004/12/31 09:00 [medline] PHST- 2004/11/06 09:00 [entrez] AID - JID32710 [pii] AID - 10.1086/425519 [doi] PST - ppublish SO - J Infect Dis. 2004 Dec 1;190(11):2010-9. doi: 10.1086/425519. Epub 2004 Nov 3.