Universität zu Köln

Farowski, Fedja, Cornely, Oliver A. and Hartmann, Pia (2016). High Intracellular Concentrations of Posaconazole Do Not Impact on Functional Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived Macrophages In Vitro. Antimicrob. Agents Chemother., 60 (6). S. 3533 - 3540. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-6596

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Abstract

Posaconazole is a commonly used antifungal for the prophylaxis and treatment of invasive fungal infections. We previously demonstrated that the intracellular concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma concentration. As these professional phagocytes are crucial to combat fungal infections, we set out to investigate if and how, beneficial or deleterious, this high loading of intracellular posaconazole impacts the functional capacities of these cells. Here, we show that high intracellular concentrations of posaconazole do not significantly impact PMN and monocyte-derived macrophage function in vitro. In particular, killing capacity and cytoskeletal features of PMN, such as migration, are not affected, indicating that these cells serve as vehicles for posaconazole to the site of infection. Moreover, since posaconazole as such slowed the germination of Aspergillus fumigatus conidia, infected neutrophils released less reactive oxygen species (ROS). Based on these findings, we propose that the delivery of posaconazole by neutrophils to the site of Aspergillus species infection warrants control of the pathogen and preservation of tissue integrity at the same time.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Farowski, Fedja UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, Oliver A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-273749
DOI:	10.1128/AAC.02060-15
Journal or Publication Title:	Antimicrob. Agents Chemother.
Volume:	60
Number:	6
Page Range:	S. 3533 - 3540
Date:	2016
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-6596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ASPERGILLUS-FUMIGATUS CONIDIA; ALVEOLAR MACROPHAGES; PERIPHERAL-BLOOD; INVITRO; EPIDEMIOLOGY; ITRACONAZOLE; COMPARTMENTS; FLUCONAZOLE; RESISTANCE; LEUKOCYTES Multiple languages Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27374