AAC
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Larabi, M.
Right arrow Articles by Barratt, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Larabi, M.
Right arrow Articles by Barratt, G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2001, p. 553-562, Vol. 45, No. 2
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.2.553-562.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Reduction of NO Synthase Expression and Tumor Necrosis Factor Alpha Production in Macrophages by Amphotericin B Lipid Carriers

Malika Larabi,1 Philippe Legrand,1 Martine Appel,1 Sophie Gil,2 Michel Lepoivre,3 Jean-Philippe Devissaguet,1 Francis Puisieux,1 and Gillian Barratt1,*

Laboratoire de Physico-Chimie-Pharmacotechnie-Biopharmacie, UMR CNRS 8612,1 and Laboratoire de Biochimie, INSERM U 461,2 Université Paris XI, 92296 Châtenay Malabry Cedex, and UMR CNRS 8619, Université Paris XI, 91405 Orsay Cedex,3 France

Received 8 August 2000/Returned for modification 2 October 2000/Accepted 19 November 2000

The present study compared the abilities of different lipid carriers of amphotericin B (AMB) to activate murine peritoneal macrophages, as assessed by their capacities to produce nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha ). Although AMB alone did not induce NO production, synergy was observed with gamma interferon but not with lipopolysaccharide. This synergy could not be explained by the mobilization of the nuclear activation factor NF-kappa B by AMB. On the other hand, AMB induced TNF-alpha production without a costimulator and no synergy was observed. Anti-TNF-alpha antibodies did not influence NO production, and an inhibitor of NO synthase did not affect TNF-alpha production, indicating that the production of one of these effector molecules was independent of that of the other. The incorporation of AMB into lipid carriers reduced NO and TNF-alpha production with all formulations but more so with liposomes than with lipid complexes. NO production was correlated with the induction of NO synthase II, revealed by Western blotting. The extent of association of AMB with macrophages depended on the formulation, especially on the AMB/lipids ratio: the higher the ratio was, the greater the AMB association with macrophages. However, there was no clear correlation between AMB association with macrophages, whether internalized or bound to the membrane, and immunostimulating effects. These results may explain the reduced toxicities of lipid-based formulations of AMB.

* Corresponding author. Mailing address: UMR CNRS 8612, Faculty of Pharmacy, 5 rue Jean Baptiste Clément, 92296 Châtenay- Malabry Cedex, France. Phone: (33) (0) 1 46 83 56 27. Fax: (33) (0) 1 46 61 93 34. E-mail: Gillian.Barratt{at}cep.u-psud.fr.

Antimicrobial Agents and Chemotherapy, February 2001, p. 553-562, Vol. 45, No. 2
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.2.553-562.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Clin. Vaccine Immunol. Clin. Microbiol. Rev.
J. Clin. Microbiol. ALL ASM JOURNALS

Copyright © 2001 by the American Society for Microbiology. All rights reserved.