Document Detail


Peroxovanadium-mediated protection against murine leishmaniasis: role of the modulation of nitric oxide.
MedLine Citation:
PMID:  11009089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The phosphotyrosine phosphatase inhibitor bpV(phen) has the ability to markedly decrease the progression of leishmaniasis in vivo. Here, we have identified the mechanisms that are responsible for this protective effect. We report that two potent peroxovanadium (pV) compounds, bpV(phen) and bpV(pic), control progression of leishmaniasis in a similar manner by modulating NO-dependent microbicidal action. We observed that their injection can rapidly and transiently induce the expression of inducible NO synthase (iNOS) in livers of mice and enhance circulating nitrate levels. Treatment of mice with bpV(phen) or bpV(pic) completely controlled progression of leishmaniasis in an NO-dependent manner, since inhibition of iNOS with aminoguanidine completely reversed this pV-mediated protection. This NO-dependent pV-mediated protection was further demonstrated by the incapacity of bpV(phen)-treated Nramp-/-, iNOS-/- mutant mice to control Leishmania major infection. Using an air pouch model, we showed that bpV(phen) can strongly modulate secretion of L. major-induced pro-inflammatory molecules and neutrophil recruitment. In addition, we observed that bpV(phen) per se can strongly induce the expression of Th1 type cytokines over Th2 in spleens of animals. Overall, this study has allowed us to establish the in vivo functional and immunological events involved in pV-mediated protective mechanism against leishmaniasis and that NO plays a pivotal role in this process.
Authors:
C Matte; J F Marquis; J Blanchette; P Gros; R Faure; B I Posner; M Olivier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  30     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-10-12     Completed Date:  2000-10-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  2555-64     Citation Subset:  IM    
Affiliation:
Centre de Recherche en Infectiologie and Département de Biologie Médicale, Centre Hospitalier Universitaire de Québec, Faculté de Médecine, Université Laval, Ste-Foy, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cytokines / biosynthesis,  genetics
Enzyme Inhibitors / pharmacology*
Female
Leishmaniasis / immunology,  prevention & control*
Macrophage Activation
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neutrophils / immunology
Nitric Oxide / physiology*
Nitric Oxide Synthase / physiology
Nitric Oxide Synthase Type II
Protein Tyrosine Phosphatases / antagonists & inhibitors*,  physiology
RNA, Messenger / analysis
Vanadium Compounds / pharmacology*
Chemical
Reg. No./Substance:
0/Cytokines; 0/Enzyme Inhibitors; 0/RNA, Messenger; 0/Vanadium Compounds; 10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse; EC 3.1.3.48/Protein Tyrosine Phosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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