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Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
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Uptake and intracellular activity of voriconazole in human polymorphonuclear leucocytes

Sofía Ballesta1, Isabel García, Evelio J Perea

  • 1Department of Microbiology, School of Medicine, University of Seville, Spain. mudarra@us.es

The Journal of Antimicrobial Chemotherapy
|April 13, 2005
PubMed
Abstract

Insights

Voriconazole penetrates human polymorphonuclear leucocytes (PMNs) rapidly, reaching high intracellular concentrations. However, this uptake did not enhance the intracellular killing of Candida species.

Area of Science:

  • Pharmacology and Microbiology
  • Immunology and Infectious Diseases

Background:

  • Voriconazole is a key antifungal agent.
  • Understanding voriconazole's interaction with immune cells like polymorphonuclear leucocytes (PMNs) is crucial for its clinical efficacy against Candida infections.

Purpose of the Study:

  • To evaluate the intracellular penetration of voriconazole into human PMNs.
  • To assess the intracellular antifungal activity of voriconazole against Candida species within PMNs.

Main Methods:

  • Radiometric assay used to measure voriconazole uptake by PMNs.
  • Investigated effects of cell viability, environmental conditions, metabolic inhibitors, and membrane stimulation on uptake.
  • Intracellular activity assessed by incubating PMNs with Candida blastospores and voriconazole.

Main Results:

  • Voriconazole demonstrated rapid, non-saturable uptake into PMNs with a high cellular to extracellular concentration ratio (8.5±1.3).
  • Voriconazole was quickly released from PMNs; uptake was unaffected by temperature, viability, pH, or metabolic inhibitors.
  • Ingestion of zymosan decreased PMN-associated voriconazole, but voriconazole did not affect intracellular Candida survival at tested concentrations.

Conclusions:

  • Voriconazole achieves significant intracellular concentrations within human PMNs via rapid, non-saturable uptake.
  • Despite high intracellular levels, voriconazole did not enhance the intracellular killing capacity of PMNs against Candida species.

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