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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Proteomic identification of IPSE/alpha-1 as a major Hepatotoxin secreted by Schistosoma mansoni eggs
PLoS Neglected Tropical Diseases, Volume 5, No. 10, Article e1368, Year 2011
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Description
Background: Eggs deposited in the liver of the mammalian host by the blood fluke parasite, Schistosoma mansoni, normally drive a T-helper-2 (Th2)-mediated granulomatous response in immune-competent mice. By contrast, in mice deprived of T-cells and incapable of producing granulomata, egg-secreted proteins (ESP) induce acute hepatic injury and death. Previous work has shown that one such ESP, the T2 ribonuclease known as omega-1, is hepatotoxic in vivo in that specific antisera to omega-1 prevent hepatocyte damage. Methodology/Principal Findings: Using an in vitro culture system employing mouse primary hepatocytes and alanine transaminase (ALT) activity as a marker of heptocyte injury, we demonstrated that S. mansoni eggs, egg-secreted proteins (ESP), soluble-egg antigen (SEA), and omega-1 are directly hepatotoxic and in a dose-dependent manner. Depletion of omega-1 using a monoclonal antibody abolished the toxicity of pure omega-1 and diminished the toxicity in ESP and SEA by 47 and 33%, respectively. Anion exchange chromatography of ESP yielded one predominant hepatotoxic fraction. Proteomics of that fraction identified the presence of IPSE/alpha-1 (IL-4 inducing principle from S. mansoni eggs), a known activator of basophils and inducer of Th2-type responses. Pure recombinant IPSE/alpha-1 also displayed a dose-dependent hepatotoxicity in vitro. Monoclonal antibody depletion of IPSE/alpha-1 abolished the latter's toxicity and diminished the total toxicity of ESP and SEA by 32 and 35%, respectively. Combined depletion of omega-1 and IPSE/alpha-1 diminished hepatotoxicity of ESP and SEA by 60 and 58% respectively. Conclusions: We identified IPSE/alpha-1 as a novel hepatotoxin and conclude that both IPSE/alpha-1 and omega-1 account for the majority of the hepatotoxicity secreted by S. mansoni eggs. © 2011 Abdulla et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3201919/bin/pntd.0001368.s001.doc
Authors & Co-Authors
Abdulla, Maha Hamadien
Saudi Arabia, Riyadh
King Khalid University Hospital
United States, San Francisco
University of California, San Francisco
Lim, Kee Chong
Saudi Arabia, Riyadh
King Khalid University Hospital
McKerrow, James Hobson
Saudi Arabia, Riyadh
King Khalid University Hospital
Caffrey, Conor Robert
Saudi Arabia, Riyadh
King Khalid University Hospital
Statistics
Citations: 47
Authors: 4
Affiliations: 2
Identifiers
Doi:
10.1371/journal.pntd.0001368
ISSN:
19352727
e-ISSN:
19352735
Research Areas
Violence And Injury