Re: COMPARISON OF INFLAMMATORY RESPONCES IN MOUSE LUNGS

[Guest guest]

Great find, Jeanine!!

You guys, please forward this information of Dr. Flemming and Rand's newest

publication to those you

think would find it of interest. This one is really helpful. Tell your

attorneys and your doctors.

" 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 _

(http://taylorandfrancis.metapress.com/(s0i3txzwf2wciwntq00vxgjo)/app/home/journ\

al.asp?referrer=se

archresults & id=100675 & backto=searcharticlesresults,1,6;)

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

2006 _

(http://taylorandfrancis.metapress.com/(s0i3txzwf2wciwntq00vxgjo)/app/home/issue\

..asp?referrer=searchresults & id=N87U083N2R55 & backto=searcharticlesresults,

1,6;) Pages: 1239 - 1251 URL: _Linking Options_

(http://taylorandfrancis.metapress.com/(s0i3txzwf2wciwntq00vxgjo)/app/home/linki\

ng.asp?referrer=l

inking & target=contribution & id=R5048J37649XT10X & backto=contribution,1,1;searcha

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.

____________________________________

[Guest guest]

Thanks

SNK

-

-- In , snk1955@... wrote:

>

> Great find, Jeanine!!

>

>

> You guys, please forward this information of Dr. Flemming and

Rand's newest

> publication to those you

> think would find it of interest. This one is really helpful.

Tell your

> attorneys and your doctors.

>

>

>

> " 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 _

> (http://taylorandfrancis.metapress.com/

(s0i3txzwf2wciwntq00vxgjo)/app/home/journal.asp?referrer=se

> archresults & id=100675 & backto=searcharticlesresults,1,6;)

> Publisher: & Francis Issue: _Volume 69, Number 13 /

July 1

> 2006 _

> (http://taylorandfrancis.metapress.com/

(s0i3txzwf2wciwntq00vxgjo)/app/home/issue.asp?

referrer=searchresults & id=N87U083N2R55 & backto=searcharticlesresults,

> 1,6;) Pages: 1239 - 1251 URL: _Linking Options_

> (http://taylorandfrancis.metapress.com/

(s0i3txzwf2wciwntq00vxgjo)/app/home/linking.asp?referrer=l

>

inking & target=contribution & id=R5048J37649XT10X & backto=contribution,1,1

;searcha

> 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.

>

> ____________________________________

>

>

>

>