Aspergillus lipoxygenase : a novel instigator of asthma ?

Ref ID: 19617

Author:

GJ Fischer1*, J Yang2, J Palmer3$, T Dagenais3, X Huang4, B Hammock2, NP Keller1,3

Author address:

1Department of Genetics, University of Wisconsin-Madison, USA
2Department of Entomology, University of California-Davis, USA
3Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, USA
4 UCSF Sandler Asthma Basic Resea

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Fungi have long been associated with asthmatic/allergy diseases, yet the exact mechanism(s) by which
fungi induce asthma is unknown. Human 5-lipoxygenase derived oxylipins, including leukotrienes,
induce inflammation, mucus secretion, vasodilation, immune cell recruitment, and bronchial
constriction. Increasing evidence suggests that specific oxylipins play critical roles in exacerbating
asthmatic phenotypes, with significant differences in oxylipin profiles between asthmatics and
non-asthmatics. We investigated the ability of an Aspergillus fumigatus lipoxygenase, LoxB, to
synthesize oxylipins similar to those detected in humans and whether those oxylipin products could
exacerbate acute allergic responses commonly associated with asthma.
Methods:
We identified a 5-lipoxygenase homolog, LoxB, within Aspergillus fumigatus. loxB deletion and
overexpression strains were grown in RPMI media and culture supernatant assessed for oxylipin
production using mass spectrometry (n=3). Fungal extract/oxylipin cocktails were prepared by
mixing 1:1 oxylipin-containing culture supernatant and soluble antigenic extract solution prepared
from the fungal tissue of each respective loxB strain. Cocktail solution was administered to mice (n=9)
three times a week over a three week period after which differences in airway hyperresponsiveness,
immune cell recruitment, and IgE production were recorded.
Results:
Overexpression of LoxB leads to increased production of several oxylipins known to cause
airway hyperresponsiveness including hydroxyeicosatetraenoic acids (HETEs) from the human
5-lipoxygenase pathway and hydroxyoctadecanoic acids (HODEs). Murine asthma studies
demonstrated that mice treated with fungal cocktail derived from the overexpression loxB strain
exhibit elevated airway hyperresponsiveness, increased macrophage and eosinophil recruitment,
and higher IgE levels than mice administered wild-type or loxB deletion-derived fungal cocktail.
Conclusions:
This study demonstrates the ability of fungal lipoxygenases to exacerbate acute allergic responses.
We propose that A. fumigatus LoxB is involved in asthmatic diseases, particularly ABPA (Allergic
bronchopulmonary aspergillosis). Future work includes characterizing the oxylipins responsible for
the acute allergic responses and assessing the impact of other A. fumigatus oxygenases and resultant
oxylipins on asthmatic and allergenic responses.
NOTE: THIS ABSTRACT HAS BEEN SELECTED FOR ORAL PRESENTATION.

Abstract Number: 142

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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