Am. J. Respir. Cell Mol. Biol.,
Volume 26, Number 6, June, 2002 685-693
Iron Loading Makes a Nonfibrogenic Model Air Pollutant Particle
Fibrogenic In Rat Tracheal Explants
Jin
Dai,
Changshie
Xie,
and
Andrew
Churg
Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada
To examine the potential role of particle iron in fibrogenicity,
we loaded nonfibrogenic fine (0.12µ) TiO2 with increasing amounts of Fe(II)-Fe(III) chloride. Dusts were applied to rat tracheal explants, which were maintained in air organ culture for 1 wk. Iron-loaded dust increased procollagen gene expression and tissue hydroxyproline. The active oxygen species
(AOS) scavenger tetramethylthiourea prevented these effects.
Iron loading caused nuclear factor (NF)- B activation, decreased levels of total IB , but relatively increased levels of
both IB-phosphoserine 32/36 and IB-phosphotyrosine. A
citrate extract of iron-loaded dust increased procollagen expression. Gel shift using a probe consisting of the NF-B consensus sequence from the prolyl-4-hydroxylase promoter and
adjacent bases showed increased nuclear binding, and RT-PCR
examination showed increased prolyl-hydroxylase -chain gene
expression after iron loading. We conclude that addition of
surface iron can convert a nonreactive model air pollutant particle into a fibrogenic particle via AOS- and NF-B-dependent pathways, probably through two different NF-B activation pathways in two different anatomic compartments. This
process may proceed in vivo through iron extracted from the
dust into the cytoplasm. NF-B activation may directly increase expression of prolyl hydroxylase, an enzyme involved
in collagen synthesis. These findings suggest that air pollutant
particles containing significant quantities of transition metals
may produce airway wall fibrosis and lead to chronic obstructive pulmonary disease.
Abbreviations: active oxygen species, AOS; chronic obstructive pulmonary disease, COPD; deferoxamine, DFX; Dulbecco's modified Eagle's
medium, DMEM; interleukin, IL; platelet-derived growth factor, PDGF;
prolyl-4-hydroxylase, PH; respirable air pollutant particles, PM; nuclear
factor-B, NF-B; residual oil fly ash, ROFA; reverse transcriptase-polymerase chain reaction, RT-PCR; tris-buffered saline, TBS; transforming
growth factor, TGF; tetramethylthiourea, TMTU; tumor necrosis factor, TNF.
This article has been cited by other articles:
|
|
|
|
 
R. D. Wang, J. L. Wright, and A. Churg
Transforming Growth Factor-{beta}1 Drives Airway Remodeling in Cigarette Smoke-Exposed Tracheal Explants
Am. J. Respir. Cell Mol. Biol.,
October 1, 2005;
33(4):
387 - 393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Ghio, A. Churg, and V. L. Roggli
Review: Ferruginous Bodies: Implications in the Mechanism of Fiber and Particle Toxicity
Toxicol Pathol,
October 1, 2004;
32(6):
643 - 649.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Boehler and M. Estenne
Post-transplant bronchiolitis obliterans
Eur. Respir. J.,
December 1, 2003;
22(6):
1007 - 1018.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Wang, H. Tai, C. Xie, X. Wang, J. L. Wright, and A. Churg
Cigarette Smoke Produces Airway Wall Remodeling in Rat Tracheal Explants
Am. J. Respir. Crit. Care Med.,
November 15, 2003;
168(10):
1232 - 1236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Dai, C. Xie, R. Vincent, and A. Churg
Air Pollution Particles Produce Airway Wall Remodeling in Rat Tracheal Explants
Am. J. Respir. Cell Mol. Biol.,
September 1, 2003;
29(3):
352 - 358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Upadhyay, V. Panduri, A. Ghio, and D. W. Kamp
Particulate Matter Induces Alveolar Epithelial Cell DNA Damage and Apoptosis: Role of Free Radicals and the Mitochondria
Am. J. Respir. Cell Mol. Biol.,
August 1, 2003;
29(2):
180 - 187.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2002 American Thoracic Society.
|
|
|
