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@ARTICLE{CampiSantos:284097,
author = {Campi Santos, Patricia and Santos, Daniel Assis and Secchim
Ribeiro, Lucas and Fagundes, Caio Tavares and de Paula,
Talles Prosperi and Avila, Thiago Vinícius and Baltazar,
Ludmila de Matos and Madeira, Mila Moreira and Cruz, Rosana
de Carvalho and Dias, Ana Carolina Fialho and Machado,
Fabiana Simão and Teixeira, Mauro Martins and Cisalpino,
Patrícia Silva and Souza, Danielle G.},
title = {{T}he {P}ivotal {R}ole of 5-{L}ipoxygenase-{D}erived {LTB}4
in {C}ontrolling {P}ulmonary {P}aracoccidioidomycosis},
journal = {PLoS neglected tropical diseases},
volume = {7},
number = {8},
issn = {1935-2727},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {DZNE-2026-00105},
pages = {e2390},
year = {2013},
abstract = {Leukotrienes (LTs) produced from arachidonic acid by the
action of 5-lipoxygenase (5-LO) are classical mediators of
inflammatory responses. However, studies published in the
literature regarding these mediators are contradictory and
it remains uncertain whether these lipid mediators play a
role in host defense against the fungal pathogen
Paracoccidioides brasiliensis. To determine the involvement
of LTs in the host response to pulmonary infection,
wild-type and LT-deficient mice by targeted disruption of
the 5-lipoxygenase gene (knockout mice) were studied
following intratracheal challenge with P. brasiliensis
yeasts. The results showed that infection is uniformly fatal
in 5-LO-deficient mice and the mechanisms that account for
this phenotype are an exacerbated lung injury and higher
fungal pulmonary burden. Genetic ablation or pharmacological
inhibition of LTs resulted in lower phagocytosis and
fungicidal activity of macrophages in vitro, suggesting that
deficiency in fungal clearance seems to be secondary to the
absence of activation in 5-LO(-/-) macrophages. Exogenous
LTB4 restored phagocytosis and fungicidal activity of
5-LO(-/-) macrophages. Moreover, P. brasiliensis killing
promoted by LTB4 was dependent on nitric oxide (NO)
production by macrophages. Taken together, these results
reveal a fundamental role for 5-LO-derived LTB4 in the
protective response to P. brasiliensis infection and
identify relevant mechanisms for the control of fungal
infection during the early stages of the host immune
response.},
keywords = {Animals / Arachidonate 5-Lipoxygenase: metabolism / Colony
Count, Microbial / Disease Models, Animal / Leukotriene B4:
metabolism / Lung: microbiology / Lung: pathology / Male /
Mice / Mice, Knockout / Paracoccidioides: immunology /
Paracoccidioidomycosis: immunology / Survival Analysis /
Leukotriene B4 (NLM Chemicals) / Arachidonate 5-Lipoxygenase
(NLM Chemicals)},
ddc = {610},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
doi = {10.1371/journal.pntd.0002390},
url = {https://pub.dzne.de/record/284097},
}