Document Detail


Amphotericin B inhibits entry of Leishmania donovani into primary macrophages.
MedLine Citation:
PMID:  20678487     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Visceral leishmaniasis is a vector-borne disease caused by an obligate intra-macrophage protozoan parasite Leishmania donovani. The molecular mechanisms involved in internalization of Leishmania are still poorly understood. Amphotericin B and its formulations are considered as the best existing drugs against visceral leishmaniasis and are being increasingly used. The reason for its antileishmanial activity is believed to be its ability to bind ergosterol found in parasite membranes. In case of in vivo amphotericin B treatment, both host macrophages and parasites are exposed to amphotericin B. The effect of amphotericin B treatment could therefore be due to a combination of its interaction with both sterols i.e., ergosterol of Leishmania and cholesterol of host macrophages. We report here that cholesterol complexation by amphotericin B markedly inhibits binding of L. donovani promastigotes to macrophages. These results represent one of the first reports on the effect of amphotericin B on the binding of Leishmania parasites to host macrophages. Importantly, these results offer the possibility of reevaluating the mechanism behind the effectiveness of current therapeutic strategies that employ sterol-complexing agents such as amphotericin B to treat leishmaniasis.
Authors:
Yamuna Devi Paila; Bhaskar Saha; Amitabha Chattopadhyay
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-03
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  399     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2010-09-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  429-33     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India.
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MeSH Terms
Descriptor/Qualifier:
Amphotericin B / pharmacology*,  therapeutic use
Animals
Antiprotozoal Agents / pharmacology*,  therapeutic use
Female
Leishmania donovani / drug effects*,  physiology
Leishmaniasis, Visceral / drug therapy
Macrophages, Peritoneal / drug effects*,  parasitology
Mice
Mice, Inbred BALB C
Chemical
Reg. No./Substance:
0/Antiprotozoal Agents; 1397-89-3/Amphotericin B

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