S.Chartarum could contribute to inflammatory lung disease

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" Data also suggest that exposure to these toxins in spores of S.

chartarum

in contaminated building environments could contribute to

inflammatory lung

disease onset in susceptible individuals. "

_Journal of Toxicology and Environmental Health Part A _

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Publisher: & Francis Issue: _Volume 69, Number 13 / July 1

2006 _

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rticlesresults,1,6;) DOI: 10.1080/15287390500360307

Comparison of Inflammatory Responses in Mouse Lungs Exposed to

Atranones A

And C from Stachybotrys Chartarum

G. Rand A1, J. Flemming A1, J. A2, Taiwo O.

Womiloju A2

A1 Department of Biology, Saint 's University, Halifax, Nova

Scotia,

Canada

A2 Department of Chemistry, Carleton University, Ottawal, Ontario,

Canada

Abstract:

Stachybotrys chartarum isolates can be separated into two distinct

chemotypes based on the toxins they produce. One chemotype produces

macrocyclic

trichothecenes; the other produces atranones (and sometimes simple

trichothecenes,

e.g., trichodermol and trichodermin). Studies using in vivo models

of lung

disease revealed that exposure to spores of the atranone producing S.

chartarum isolates led to a variety of immunotoxic, inflammatory,

and other

pathological changes. However, it is unclear from these studies what

role the

pure

atranone toxins sequestered in spores of these isolates exert on

lung disease

onset. This study examined dose-response (0.2, 1.0, 2.0, 5.0, or 20

μg

atranone/animal) and time-course (3, 6, 24, and 48 h

postinstillation [PI])

relationships associated with inflammatory cell and proinflammatory

chemokine/cytokine responses in mouse lungs intratracheally

instilled with two

pure atranones

(either A or C) isolated from S. chartarum. High doses (2.0 to 20 μg

toxin/animal) of atranone A and C induced significant inflammatory

responses

manifested as differentially elevated macrophage, neutrophil,

macrophage

inflammatory protein (MIP)-2, tumor necrosis factor (TNF) and

interleukin

(IL)-6

concentrations in the bronchioalveolar lavage fluid (BALF) of

intratracheally

exposed mice. Compared to controls, BALF macrophage and neutrophil

numbers

were

increased to significant levels from 6 to 48 h (PI). Except for

macrophage

numbers in atranone A treatment animals, cells exhibited significant

dose

dependent-like responses. The chemokine/cytokine marker responses

were

significantly and dose-dependently increased from 3 to 24 h PI and

declined to

nonsignificant levels at 48 h PI. The results suggest not only that

atranones

are

inflammatory but also that they exhibit different inflammatory

potency with

different toxicokinetics. Data also suggest that exposure to these

toxins in

spores of S. chartarum in contaminated building environments could

contribute

to

inflammatory lung disease onset in susceptible individuals.