Environmental Engineering Reference
In-Depth Information
Zelikoff et al. (
2002
) conducted a series of studies to investigate reports from
epidemiologic studies that exposure to ambient PM is associated with increased
respiratory infections, especially in elderly individuals. Fischer 344 rats that had
been previously infected with
Streptococcus pneumoniae
were exposed for 5 h in an
inhalation chamber to ambient New York City PM
2.5
(65-90
g/m
3
) or fi ltered air.
In another set of studies, previously infected rats and uninfected controls were
exposed by inhalation to chloride salts of Fe, Mn, or Ni at a concentration of
65-90
ʼ
g/m
3
for 5 h. Rats were sacrifi ced at various intervals after exposure and
examined for signs of
S. pneumoniae
infection and markers of infl ammation in
BALF and blood. By 18 h post-exposure, bacterial burdens in the lungs of rats
exposed to the NYC PM
2.5
were signifi cantly greater (300 times, p < 0.01) than fi l-
tered air controls, and the number of pulmonary lymphocytes (cells responsible for
bacterial pathogen removal) in PM-exposed animals was lower than in controls
(p < 0.05). Exposure to the individual transition metals altered some pulmonary and
systemic immune system parameters in uninfected rats. Exposure to Fe or Ni (at
≥
ʼ
1,000-fold higher than ambient air), but not Mn signifi cantly altered bacterial
clearance. The authors suggested that Fe and Ni in ambient PM may play a role in
exacerbating bacterial lung infections.
Zhou et al. (
2003
) conducted an acute pulmonary inhalation exposure study to
determine the association between exposure to Fe in ultrafi ne PM and adverse pul-
monary response. Healthy rats were exposed to ultrafi ne Fe particulate (57 or 90
g/
m
3
, median particle diameter 72 nm) or fi ltered air for 6 h/day for 3 consecutive
days. Rats were euthanized within 2 h of fi nal exposure and markers of infl amma-
tion and injury in BALF and lung homogenate were quantifi ed. Exposure at a con-
centration of 57
ʼ
g/m
3
of Fe did not elicit signifi cant responses that were different
from controls. Exposure at the highest dose, 90
ʼ
g/m
3
, was signifi cantly associated
with increased ferritin expression (p < 0.05, indicates bioavailable iron), total pro-
tein (p < 0.05, indicator of cytotoxicity), IL-1B (p < 0.01, marker of infl ammation)
and an increase in markers of oxidative stress in the lungs (p < 0.01). The authors
concluded that inhaled Fe in ultrafi ne particles is bioavailable and is associated with
adverse pulmonary effects in rats and that this association appears to be dose-
dependent. However, the dose administered in this study that elicited an adverse
response was over 900 times higher than ambient concentrations in PM
2.5
(Table
1
),
and ultrafi ne particles comprise an extremely small fraction (by mass) of PM
2.5
.
Ghio et al. (
2005
) explored the role of the transferrin-independent surface protein,
divalent metal transporter-1 (DMT-1), and its role in detoxifi cation of Fe in the lung.
Homozygous Belgrade rats demonstrate poor Fe absorption and resulting anemia.
DMT-1-defi cient rats were exposed to either 0.5 mL saline or 500
ʼ
g of ROFA in
0.5 mL saline via intratracheal instillation. In another phase of the study, normal
Sprague Dawley rats were instilled with 0.5 mL of saline, 0.5 mL of 100
ʼ
ʼ
M ferric
ammonium citrate, or 0.5 mL of 10
M vanadyl sulfate. After 24 h, the same rats
were again anesthetized and instilled with either saline or 500
ʼ
g ROFA in saline.
Sacrifi ces were then made at 15, 30, or 60 min and/or 24 h after the second instilla-
tion, and lungs were then analyzed for Fe and V. At 24 h post exposure, homozygous
ʼ
Search WWH ::
Custom Search