Hypoxia in Leishmania major Skin Lesions Impairs the NO-Dependent Leishmanicidal Activity of Macrophages
| Autor: | Christian Bogdan, Jonathan Jantsch, Kirstin Castiglione, Alexander Mahnke, Valentin Schatz, Robert J. Meier, Otto S. Wolfbeis, Ulrike Schleicher, Julian Hofmann |
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| Rok vydání: | 2014 |
| Předmět: |
Atmosphere Exposure Chambers
Leishmaniasis Cutaneous Nitric Oxide Synthase Type II chemistry.chemical_element Dermatology Nitric Oxide Biochemistry Parasite load Oxygen Lesion parasitic diseases medicine Animals Leishmania major Hypoxia Molecular Biology Skin Mice Knockout Mice Inbred BALB C Arginase ATP synthase biology Macrophages Cell Biology respiratory system Hypoxia (medical) biology.organism_classification Leishmania Molecular biology Phenotype Mice Inbred C57BL chemistry Immunology biology.protein medicine.symptom |
| Zdroj: | Journal of Investigative Dermatology. 134:2339-2346 |
| ISSN: | 0022-202X |
| Popis: | Cure of infections with Leishmania major is critically dependent on the ability of macrophages to induce the type 2 nitic oxide (NO) synthase (NOS2) that produces high levels of NO in the presence of ample oxygen. Therefore, we analyzed the oxygen levels found in leishmanial skin lesions and their effect on the NOS2-dependent leishmanicidal activity of macrophages (MΦ). When L. major skin lesions of self-healing C57BL/6 mice reached their maximum size, the infected tissue displayed low oxygen levels ( p O 2 ~21Torr). MΦ activated under these oxygen tensions failed to produce sufficient amounts of NO to clear L. major . Nos2 -deficient and hypoxic wild-type macrophages displayed a similar phenotype. Killing was restored when MΦ were reoxygenated or exposed to a NO donor. The resolution of the lesion in C57BL/6 mice was paralleled by an increase of lesional p O 2 . When mice were kept under normobaric hypoxia, this caused a persistent suppression of the lesional p O 2 and a concurrent increase of the parasite load. In Nos2 -deficient mice, there was no effect of atmospheric hypoxia. Low oxygen levels found at leishmanial skin lesions impaired the NOS2-dependent leishmanicidal activity of MΦ. Hence, tissue oxygenation represents an underestimated local milieu factor that participates in the persistence of Leishmania . |
| Databáze: | OpenAIRE |
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