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ABSTRACT |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Elevated levels of ambient particulate matter (PM10) have been associated with increased cardiopulmonary morbidity and mortality. We previously showed that the deposition of particles in the lung induces a systemic inflammatory response that includes stimulation of the bone marrow. This marrow response is related to mediators released by alveolar macrophages (AM) and in this study we
measured cytokines produced by human AM exposed to ambient
particles of different composition and size. Identified cytokines
were also measured in the circulation of healthy young subjects
exposed to air pollutants during the 1997 Southeast Asian forest
fires. Human AM were incubated with particle suspensions of residual oil fly ash (ROFA), ambient urban particles (EHC 93), inert
carbon particles, and latex particles of different sizes (0.1, 1, and 10 µm) and concentrations for 24 h. Tumor necrosis factor-alpha (TNF-
) increases in a dose-dependent manner when AM were exposed to EHC 93 particles (p < 0.02). The TNF response of AM exposed to different sizes of latex particles was similar. The latex
(158 ± 31%), inert carbon (179 ± 32%), and ROFA (216 ± 34%)
particles all show a similar maximum TNF response (percent
change from baseline) whereas EHC 93 (1,020 ± 212%, p < 0.05)
showed a greater maximum response that was similar to lipopolysaccharide (LPS) 1 µg/ml (812 ± 320%). Macrophages incubated with an optimal dose of EHC 93 particles (0.1 mg/ml) also
produce a broad spectrum of other proinflammatory cytokines,
particularly interleukin (IL)-6 (p < 0.01), IL-1
(p < 0.05), macrophage inflammatory protein-1 (MIP-1) (p < 0.05), and granulocyte macrophage colony-stimulating factor (GM-CSF) (p < 0.01)
with no difference in concentrations of the anti-inflammatory cytokine IL-10 (p = NS). Circulating levels of IL-1, IL-6, and GM-CSF
were elevated in subjects exposed to high levels of PM10 during an
episode of acute air pollution. These results show that a range of
different particles stimulate AM to produce proinflammatory cytokines and these cytokines are also present in the blood of subjects during an episode of acute atmospheric air pollution. We
postulate that these cytokines induced a systemic response that
has an important role in the pathogenesis of the cardiopulmonary
adverse health effects associated with atmospheric pollution.
Keywords: air pollution; interleukin-6; granulocyte macrophage colony-stimulating factor; cytokines
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Epidemiologic studies have identified significant associations
between ambient air particles, especially particles with a mass
median diameter of less than 10 µm (PM10), and increased cardiopulmonary morbidity and mortality (1). The biologic mechanisms responsible for this particle-induced increase in morbidity and mortality are unclear. Seaton and colleagues postulated
that the inhalation of fine particles provokes a low-grade inflammatory response in the lung that aggravates lung disease and a
change in blood coagulability that increased pulmonary and cardiovascular deaths (4). Alveolar macrophages (AM) are the
most likely link between the inflammatory process in the lung
and the systemic response because they are cells responsible for
ingesting and clearing inhaled particles (5). The interaction of
AM with atmospheric particles increases their phagocytic activity, oxidant production, and the release of inflammatory mediators such as tumor necrosis factor-alpha (TNF-) (6, 7).
An intriguing aspect of the epidemiologic data is that the particle health effects are also associated with disease of the cardiovascular system (1) that does not come in direct contact with the particles. Studies from our laboratory have shown that particle exposure causes a leukocytosis in humans (8) and animals (9), suggesting that a systemic inflammatory response is a feature of breathing polluted air. The instillation of mediators from AM exposed to PM10 ex vivo produced a bone marrow response similar to that produced by instilling the particles themselves into the lung (9, 10). This suggests that AM are capable of initiating both a local and systemic inflammatory response when PM10 are deposited in the lung.
The activation and mobilization of inflammatory cells (9, 10), the production of acute-phase proteins (11), and the production of circulating inflammatory mediators characterize the systemic inflammatory response. An integral component of this response is stimulation of the hematopoietic system, specifically the bone marrow that results in an increase in circulating leukocytes. Several large population-based studies have shown this level of leukocytosis is a predictor of total mortality, independent of smoking (12, 13). Military recruits exposed to high concentrations of particulate matter air pollution during the forest fires in Southeast Asia in 1997, developed leukocytosis that was associated with bone marrow stimulation (8). We postulate that atmospheric particles stimulate AM to produce mediators that are capable of eliciting a systemic inflammatory response.
The present study was designed to survey the cytokines produced by human AM exposed to particles of different kinds (14- 16) and determine which of these cytokines were detectable in the blood of subjects during the Southeast Asian haze of 1997.
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METHODS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Particles
The urban air dust preparation, EHC 93, was obtained from Environmental Health Directorate, Health Canada, Ottawa, Ontario (15, 16). Residual oil fly ash (ROFA) was a kind donation by Dr. Dan Costa, Environmental Protection Agency, NC. Latex beads of different sizes (< 0.1 µm, ~ 1 µm and ~ 10 µm) were obtained from Sigma (St. Louis, MO) and inert carbon particles from Fount India Drawing Ink (Pelikan, Germany) (see details in the online data supplement).
AM
Human AM were harvested from bronchoalveolar lavage (BAL) fluid
from a noninvolved segment or lobe of lungs resected for small peripheral tumors (n = 16). Human AM harvested were more than 90%
viable (trypan blue exclusion); cells consisted of 98% AM and 2% lymphocytes and neutrophils. All specimens were tested for endotoxin
contamination using the Limulus amebocyte lysate test (E-TOXATE;
Sigma Chemical Co., St. Louis, MO) and rejected if positive. The particles (0.01 to 0.1 mg/ml) were suspended in RPMI-1640 and 10% fetal
calf serum, sonicated, and gently mixed for 20 min. Human AM (0.5 × 106/ml) were incubated with particles in a time (2, 4, 8, 12, and 24 h)
and concentration fashion at 37° C in 5% CO2 in a 24-well plate. AM
from the same subject was used as a control and incubated with the
vehicle without the particles. Supernatants were harvested, filtered
through 0.2-µm filters to remove suspended particles, and centrifuged
at 10,000 rpm for 10 min before storage at 
70° C.
Circulating Cytokine in PM10-exposed Subjects
Serum samples were collected from 30 healthy males (age 19 to 24)
who performed compulsory national service in Singapore during the
forest fires in Southeast Asia in 1997. The details of this exposure are
described elsewhere (8). Samples were collected during the haze period (September-October) and after the haze had cleared (November-December). Serum samples were frozen and kept at 70° C and
cytokine concentrations measured in batch by ELISA (see details in
online data supplement).
Statistical Analysis
All values are expressed as mean ± SEM. Differences in TNF- with
different doses of particles were evaluated with a one-way analysis of
variance (ANOVA) followed by Bonferroni correction for multiple
comparisons. Differences between control and particle-exposed AM
cytokine production were analyzed using a two-way paired t test and
corrections were done for multiple comparisons. A value of p < 0.05 was accepted as statistically significant.
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RESULTS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Particles
The elemental composition of the EHC 93 particles was previously reported by Vincent and colleagues (15). EHC 93 particles contain small amounts of endotoxin (7, 15, 17), but the dose used in this study (0.1 mg/ml) contains just trace amounts of endotoxin (< 2 ng), and this dose has been shown not to cause either a local or systemic effect when instilled into the lung of rabbits (10).
Subjects
Table 1 summarizes the demographic data of subjects from whom the AM were harvested for exposure to EHC 93. Subjects were divided into current smokers and nonsmokers (four never-smokers and one subject who stopped 22 yr before surgery). All the subjects were advised to stop smoking at least 4 wk before the surgery. Diffusing capacity of the lungs for carbon monoxide (DLCO) was reduced to 67 ± 5.1% of predicted in the smokers.
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Phagocytosis of Particles by AM
AM incubated with the smaller latex beads (0.1 and 1 µm) internalize the smaller beads and more than 80% were fluorescent-labeled. The larger beads (10 µm) just adhere to the cells.
Particles were visible in 25 ± 6% of AM incubated with a low
dose (0.01 mg/ml) of EHC 93 and 56 ± 9% with a high dose
(0.1 mg/ml) of EHC 93 showing a dose-dependent internalization of particles. Both EHC 93 and ROFA in doses higher
than 0.1 mg/ml are toxic to AM (reduced trypan blue exclusion and TNF- production, data not shown).
TNF- Produced by AM
AM stimulated with either lipopolysaccharide (LPS) or incubated with particles have maximum TNF- production after a
24-h culture period, and all values are from supernatants collected after 24 h. Incubation of AM with LPS causes a dose-dependent increase in TNF- production (see Figure E1 in the
online data supplement). AM incubated with latex beads (n = 4) produced a small but dose-dependent increase of TNF-
that was independent of the size of the beads (0.1 µm = 121 ± 8%, 1 µm = 158 ± 31%, and 10 µm = 141 ± 20%, percent
change from control). EHC 93 caused a dose-dependent increase in TNF- by AM (Figure 1a, n = 5) that was also seen
with ROFA (n = 7) and inert carbon particles (n = 3, data not
shown). Figure 1b shows the maximum TNF- response produced by the different particles (0.1 mg/ml) in comparison to
AM incubated with 1 µg/ml LPS.
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Cytokines produced by AM Incubated with EHC 93
Figures 1c and 1d show cytokines produced by human AM incubated with 0.1 mg/ml EHC 93 for 24 h. These results show a
generalized increase in all cytokine produced by AM in both
the smoker (Figure 1d) and the nonsmoker (Figure 1c) groups.
The magnitude of increase was similar in smokers and nonsmokers. There were significantly higher values for granulocyte
macrophage colony-stimulating factor (GM-CSF), interleukin-6
(IL-6), interleukin-1 (IL-1), and macrophage inflammatory
protein-1 (MIP-1) in the AM exposed to particles in the
smokers and GM-CSF, IL-6, and IL-1 in the nonsmokers.
Circulating Cytokines in PM10-exposed Subjects
All subjects were male, seven (23%) were smokers, and the average age was 21 ± 1.7 yr. Air pollution and blood cell count data during and after the haze were previously published (8). The predominant pollutant during the haze period was PM10 that showed an increase of approximately 300% (125.4 ± 44.9 versus 40 ± 14.3 µg/m3, haze versus posthaze). Other air pollutants such as SO2 (~ 190%), NO2 (~ 129%), O3 (163%), and CO (~ 131%) were also increased but to a lesser extent (8).
Figure 2a shows the concentrations of TNF, IL-1, IL-6,
and GM-CSF in the serum samples. Only values that were in
the detection range of the assay were used (TNF- 3.9 to 250 pg/ml, IL-1 0.781 to 50 pg/ml, IL-6 1.56 to 100 pg/ml, and
GM-CSF 2.344 to 150 pg/ml). IL-1 concentrations in the
blood significantly decreased after clearing of the haze (p < 0.05) with a trend toward lower concentrations of IL-6 (p = 0.09) and GM-CSF (p = 0.07). Figures 2b and 2c show the relationship between IL-1 and PM10 concentrations (Figure 2b) as well as IL-6 and PM10 concentrations (Figure 2c) during and after the haze. With clearing of the haze and a decrease in the PM10 concentrations (p < 0.001) both the circulating IL-1 and the IL-6 decreased. TNF- was similar during and after
clearing of the haze.
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DISCUSSION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Our results show that when human AM phagocytose atmospheric particles they produce TNF- in a dose-dependent
manner. When incubated with an optimal dose of atmospheric
particles (EHC 93) they also produced several other proinflammatory cytokines, particularly GM-CSF, IL-6, and IL-1.
These cytokines are known to stimulate the bone marrow to
produce and release leukocytes and platelets into the circulation (18) and stimulate the production of acute-phase proteins
(11, 18). Several of these cytokines were higher in the blood of
subjects during an acute episode of air pollution and decreased in the period after the pollution had cleared. We postulate that these cytokines found in the blood were produced by AM during phagocytosis of particles deposited in the lung. We suspect that the systemic effects of particle exposure are important in the pathogenesis of the cardiopulmonary disease
associated with particulate air pollution exposure.
AM are important in processing airborne particles and secrete mediators that are capable of eliciting both a local and a
systemic inflammatory response (5). We used TNF- as a
marker of the magnitude of AM stimulation by PM10 and
showed that incubation of human AM with different types of
particles induced a dose-dependent increase of TNF- production that was the most intense after stimulation with ambient particles collected over a major Canadian city (EHC 93).
This finding is consistent with previous reports (7, 10, 19) using different urban air pollutants. A dose of particles (EHC
93) that elicited an optimal TNF response (0.1 mg/ml) was used to investigate the nature of other cytokines produced by AM after particle exposure. In the group data (Figure 1c), the TNF response induced by an optimal dose of PM10 was not
statistically different from controls. This was due to a large
variability in the TNF response between subject both in vitro
(Figures 1c and 1d) and in vivo (Figure 2a). The endotoxin
that contaminated the particles was not responsible for this cytokine production because the particles dose used (0.1 mg/ml)
contained a very small amount of endotoxin (< 2 ng) but produced a TNF response equal to 1 µg of LPS in vitro.
Using EHC 93 to stimulate AM, we surveyed those cytokines that are known to have systemic effects and all these cytokines were increased in the supernatants of AM exposed to
particles. In smokers GM-CSF, IL-6, IL-1, and MIP-1 and
in the nonsmokers GM-CSF, IL-6, and IL-1 were significantly higher in particle-exposed compared with vehicle-exposed AM (Figures 1c and 1d). Cigarette smoking is known to
stimulate AM (20) and might confound the results we obtained in this study. However, the similar results obtained
from macrophages of smokers and nonsmokers suggest that PM10 have an independent effect on AM cytokine production.
Furthermore, seven of the 30 subjects studied during Southeast Asia haze were smokers and their bone marrow response
was similar to the nonsmokers (8), indicating that the effect of
PM10 is independent of the effect of cigarette smoking.
The cytokines produced by AM exposed to PM10 could be
of particular importance inducing the inflammatory response
associated with PM10 exposure. GM-CSF is a hematopoietic
growth factor that stimulates granulocyte and monocyte differentiation and release from the bone marrow but also activates circulating leukocytes and prolongs their survival in the
circulation (18). GM-CSF has also recently been identified to
be an important granulocyte degranulation factor that may
enhance tissue damage induced by granulocytes (21). IL-1 is
one of the "acute response" cytokines that induces cytokine
production by many cells, stimulates hematopoiesis, activates
endothelial cells, is pyrogenic, and induces the acute-phase response (18). IL-6 stimulates the liver to produce acute-phase proteins such as C-reactive protein, fibrinogen, and antiproteases by hepatic cells (11, 18); stimulates hematopoiesis, specifically the production of platelets; and has a broad stimulating effect on B and T cells (18). We have recently reported
that IL-6 accelerates the transit time of granulocytes through
the bone marrow, releases them into the circulation, and promotes their sequestration in microvascular beds (22). We also
measured IL-10, a cytokine known to inhibit the production of
proinflammatory cytokines, TNF-, IL-1, IL-6, and IL-8 from
endotoxin-stimulated human monocytes (23). The concentrations of IL-10 produced by AM exposed to PM10 did not differ
from controls (Figures 1c and 1d), suggesting that PM10 do not
induce a significant anti-inflammatory cytokine response. Collectively these three cytokines have the ability to elicit a systemic inflammatory response characterized by an increase in
circulating leukocytes, platelets, proinflammatory and prothrombotic proteins. They also have the ability to activate circulating
leukocytes and the endothelium of the vascular bed to promote
leukocyte-endothelial adhesion and migration.
Our study demonstrates that the same cytokines produced by AM exposed to urban particles (Figure 2a) were present in serum samples collected from subjects during the haze period and that their concentrations decreased after the haze cleared. This decrease in circulating cytokines correlates best with a decrease in PM10 levels (Figures 2b and 2c), suggesting that the particulate component of air pollution is important in the cytokine response induced by air pollution. Our data show that cytokines produced in the lung are present in the circulation, and we postulate that these cytokines contribute to the systemic response elicited by air pollution. Further studies are required to establish a link between circulating cytokines and the adverse cardiopulmonary effects observed in susceptible individuals exposed to air pollution.
Bioavailable metals, biogenic, organic components, and the
physical characteristics of particles have each been proposed
to be important in the PM10-induced inflammatory response in
the lung (14, 16, 24). We have used four different particles with
different physical characteristics and different organic and inorganic compositions. These different particles have no significant
difference in their ability to elicit a TNF response in AM (Figures 1b and 1c). Although the AM were able to adhere but not
engulf the larger latex particles (10 µm size), they still produced a
dose-dependent TNF response similar to AM that phagocytose smaller latex particles. This suggests that adhesion of particles to AM may initiate the signal transduction pathways responsible for cytokine production. Both ROFA (14) and EHC
93 (15) contain transitional metals that caused pulmonary injury
in healthy animals (14, 16). An increase in reactive oxygen intermediates generated by these metals has been implicated in
this tissue damage response. These oxygen intermediates also
activate nuclear factor (NF)-
B and activator protein (AP)-1,
which in turn are responsible for the subsequent induction of
various cytokine genes (25). Our results show that ambient
particles activate a broad range of cytokine genes particularly
cytokines that have the ability to induce a systemic response.
In summary, our results show that AM that phagocytoses
ambient particulate matter result in a dose-dependent increase in
TNF- production and that particles with different composition
and size produce a similar response. The AM exposed to particles also produced a broad range of other cytokines with high
concentrations of IL-6, IL-1, and GM-CSF, and these cytokines
were present in the circulation of subjects during an episode of
acute air pollution. The systemic inflammatory response that
they elicit includes the production of proinflammatory acute-phase proteins and stimulation of the bone marrow and could
be important in the pathogenesis of the pulmonary and cardiovascular disease associated with particulate air pollution.
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Footnotes |
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Correspondence and requests for reprints should be addressed to Dr. S. F. van Eeden, Pulmonary Research Laboratory, University of British Columbia, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6 Canada. E-mail: svaneeden{at}mrl.ubc.ca
(Received in original form November 1, 2000 and in revised form May 8, 2001).
Dr. van Eeden is the recipient of a Career Investigators award from the American Lung Association.This article has an online data supplement, which is accessible from this issue's table of contents online at www.atsjournals.org
Acknowledgments: The authors thank Jennifer Hards and Mark Elliott for technical support and Health Canada for making the EHC 93 available.
Supported by the British Columbia Lung Association, Canadian Institute for Health Research (Grant 4219), and the Toxic Substance Research Initiative.
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References |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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M S Goldberg, N Giannetti, R T Burnett, N E Mayo, M-F Valois, and J M Brophy A panel study in congestive heart failure to estimate the short-term effects from personal factors and environmental conditions on oxygen saturation and pulse rate Occup. Environ. Med., October 1, 2008; 65(10): 659 - 666. [Abstract] [Full Text] [PDF]
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R. L. Rouse, G. Murphy, M. J. Boudreaux, D. B. Paulsen, and A. L. Penn Soot Nanoparticles Promote Biotransformation, Oxidative Stress, and Inflammation in Murine Lungs Am. J. Respir. Cell Mol. Biol., August 1, 2008; 39(2): 198 - 207. [Abstract] [Full Text] [PDF]
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 J. R. Swiston, W. Davidson, S. Attridge, G. T. Li, M. Brauer, and S. F. van Eeden Wood smoke exposure induces a pulmonary and systemic inflammatory response in firefighters Eur. Respir. J., July 1, 2008; 32(1): 129 - 138. [Abstract] [Full Text] [PDF]
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F. M. Arantes-Costa, F. D.T.Q.S. Lopes, A. C. Toledo, P. A. Magliarelli-Filho, H. T. Moriya, R. Carvalho-Oliveira, T. Mauad, P. H. N. Saldiva, and M. A. Martins Effects of Residual Oil Fly Ash (ROFA) in Mice with Chronic Allergic Pulmonary Inflammation Toxicol Pathol, July 1, 2008; 36(5): 680 - 686. [Abstract] [Full Text] [PDF]
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 E. Tamagawa, N. Bai, K. Morimoto, C. Gray, T. Mui, K. Yatera, X. Zhang, L. Xing, Y. Li, I. Laher, et al. Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L79 - L85. [Abstract] [Full Text] [PDF]
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 K. Yatera, J. Hsieh, J. C. Hogg, E. Tranfield, H. Suzuki, C.-H. Shih, A. R. Behzad, R. Vincent, and S. F. van Eeden Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H944 - H953. [Abstract] [Full Text] [PDF]
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 N. C. Gonzalez, J. Allen, V. G. Blanco, E. J. Schmidt, N. van Rooijen, and J. G. Wood Alveolar macrophages are necessary for the systemic inflammation of acute alveolar hypoxia J Appl Physiol, October 1, 2007; 103(4): 1386 - 1394. [Abstract] [Full Text] [PDF]
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L. Calderon-Garciduenas, M. Franco-Lira, R. Torres-Jardon, C. Henriquez-Roldan, G. Barragan-Mejia, G. Valencia-Salazar, A. Gonzalez-Maciel, R. Reynoso-Robles, R. Villarreal-Calderon, and W. Reed Pediatric Respiratory and Systemic Effects of Chronic Air Pollution Exposure: Nose, Lung, Heart, and Brain Pathology Toxicol Pathol, January 1, 2007; 35(1): 154 - 162. [Abstract] [Full Text] [PDF]
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 M.-H. Cha, T. Rhim, K. H. Kim, A.-S. Jang, Y.-K. Paik, and C.-S. Park Proteomic Identification of Macrophage Migration-inhibitory Factor upon Exposure to TiO2 Particles Mol. Cell. Proteomics, January 1, 2007; 6(1): 56 - 63. [Abstract] [Full Text] [PDF]
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S. A. Ritz, J. Wan, and D. Diaz-Sanchez Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L33 - L39. [Abstract] [Full Text] [PDF]
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 A. Maitre, V. Bonneterre, L. Huillard, P. Sabatier, and R. de Gaudemaris Impact of urban atmospheric pollution on coronary disease Eur. Heart J., October 1, 2006; 27(19): 2275 - 2284. [Abstract] [Full Text] [PDF]
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A. Zeka, J. R Sullivan, P. S Vokonas, D. Sparrow, and J. Schwartz Inflammatory markers and particulate air pollution: characterizing the pathway to disease Int. J. Epidemiol., October 1, 2006; 35(5): 1347 - 1354. [Abstract] [Full Text] [PDF]
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 A. Bhatnagar Environmental Cardiology: Studying Mechanistic Links Between Pollution and Heart Disease Circ. Res., September 29, 2006; 99(7): 692 - 705. [Abstract] [Full Text] [PDF]
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 D. Aronson, I. Roterman, M. Yigla, A. Kerner, O. Avizohar, R. Sella, P. Bartha, Y. Levy, and W. Markiewicz Inverse Association between Pulmonary Function and C-Reactive Protein in Apparently Healthy Subjects Am. J. Respir. Crit. Care Med., September 15, 2006; 174(6): 626 - 632. [Abstract] [Full Text] [PDF]
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A. V. Diez Roux, A. H. Auchincloss, B. Astor, R. G. Barr, M. Cushman, T. Dvonch, D. R. Jacobs Jr., J. Kaufman, X. Lin, and P. Samson Recent Exposure to Particulate Matter and C-reactive Protein Concentration in the Multi-Ethnic Study of Atherosclerosis Am. J. Epidemiol., September 1, 2006; 164(5): 437 - 448. [Abstract] [Full Text] [PDF]
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E. Cozzi, S. Hazarika, H. W. Stallings III, W. E. Cascio, R. B. Devlin, R. M. Lust, C. J. Wingard, and M. R. Van Scott Ultrafine particulate matter exposure augments ischemia-reperfusion injury in mice Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H894 - H903. [Abstract] [Full Text] [PDF]
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 C. Chen, M. Arjomandi, H. Qin, J. Balmes, I. Tager, and N. Holland Cytogenetic damage in buccal epithelia and peripheral lymphocytes of young healthy individuals exposed to ozone Mutagenesis, March 1, 2006; 21(2): 131 - 137. [Abstract] [Full Text] [PDF]
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 Q. Sun, A. Wang, X. Jin, A. Natanzon, D. Duquaine, R. D. Brook, J.-G. S. Aguinaldo, Z. A. Fayad, V. Fuster, M. Lippmann, et al. Long-term Air Pollution Exposure and Acceleration of Atherosclerosis and Vascular Inflammation in an Animal Model JAMA, December 21, 2005; 294(23): 3003 - 3010. [Abstract] [Full Text] [PDF]
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J. Schwartz, S. K. Park, M. S. O'Neill, P. S. Vokonas, D. Sparrow, S. Weiss, and K. Kelsey Glutathione-S-Transferase M1, Obesity, Statins, and Autonomic Effects of Particles: Gene-by-Drug-by-Environment Interaction Am. J. Respir. Crit. Care Med., December 15, 2005; 172(12): 1529 - 1533. [Abstract] [Full Text] [PDF]
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Y. Tesfaigzi, J. D. McDonald, M. D. Reed, S. P. Singh, G. T. De Sanctis, P. R. Eynott, F. F. Hahn, M. J. Campen, and J. L. Mauderly Low-Level Subchronic Exposure to Wood Smoke Exacerbates Inflammatory Responses in Allergic Rats Toxicol. Sci., December 1, 2005; 88(2): 505 - 513. [Abstract] [Full Text] [PDF]
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A Zeka, A Zanobetti, and J Schwartz Short term effects of particulate matter on cause specific mortality: effects of lags and modification by city characteristics Occup. Environ. Med., October 1, 2005; 62(10): 718 - 725. [Abstract] [Full Text] [PDF]
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 H.-Y. Cho, A. E. Jedlicka, R. Clarke, and S. R. Kleeberger Role of Toll-like receptor-4 in genetic susceptibility to lung injury induced by residual oil fly ash Physiol Genomics, June 16, 2005; 22(1): 108 - 117. [Abstract] [Full Text] [PDF]
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 S. F. van Eeden, A. Yeung, K. Quinlam, and J. C. Hogg Systemic Response to Ambient Particulate Matter: Relevance to Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 61 - 67. [Abstract] [Full Text] [PDF]
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S. I. Rennard Clinical Approach to Patients with Chronic Obstructive Pulmonary Disease and Cardiovascular Disease Proceedings of the ATS, April 1, 2005; 2(1): 94 - 100. [Abstract] [Full Text] [PDF]
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 W. Q. Gan, S.F. P. Man, and D. D. Sin The Interactions Between Cigarette Smoking and Reduced Lung Function on Systemic Inflammation Chest, February 1, 2005; 127(2): 558 - 564. [Abstract] [Full Text] [PDF]
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Y. Goto, H. Ishii, J. C. Hogg, C.-H. Shih, K. Yatera, R. Vincent, and S. F. van Eeden Particulate Matter Air Pollution Stimulates Monocyte Release from the Bone Marrow Am. J. Respir. Crit. Care Med., October 15, 2004; 170(8): 891 - 897. [Abstract] [Full Text] [PDF]
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F. Gao, A. Barchowsky, A. A. Nemec, and J. P. Fabisiak Microbial Stimulation by Mycoplasma fermentans Synergistically Amplifies IL-6 Release by Human Lung Fibroblasts in Response to Residual Oil Fly Ash (ROFA) and Nickel Toxicol. Sci., October 1, 2004; 81(2): 467 - 479. [Abstract] [Full Text] [PDF]
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J. W. Hollingsworth II, D. N. Cook, D. M. Brass, J. K. L. Walker, D. L. Morgan, W. M. Foster, and D. A. Schwartz The Role of Toll-like Receptor 4 in Environmental Airway Injury in Mice Am. J. Respir. Crit. Care Med., July 15, 2004; 170(2): 126 - 132. [Abstract] [Full Text] [PDF]
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 W Q Gan, S F P Man, A Senthilselvan, and D D Sin Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis Thorax, July 1, 2004; 59(7): 574 - 580. [Abstract] [Full Text] [PDF]
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Y. Goto, J. C. Hogg, C.-H. Shih, H. Ishii, R. Vincent, and S. F. van Eeden Exposure to ambient particles accelerates monocyte release from bone marrow in atherosclerotic rabbits Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L79 - L85. [Abstract] [Full Text] [PDF]
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H. Ishii, T. Fujii, J. C. Hogg, S. Hayashi, H. Mukae, R. Vincent, and S. F. van Eeden Contribution of IL-1{beta} and TNF-{alpha} to the initiation of the peripheral lung response to atmospheric particulates (PM10) Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L176 - L183. [Abstract] [Full Text] [PDF]
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R. D. Brook, B. Franklin, W. Cascio, Y. Hong, G. Howard, M. Lipsett, R. Luepker, M. Mittleman, J. Samet, S. C. Smith Jr, et al. Air Pollution and Cardiovascular Disease: A Statement for Healthcare Professionals From the Expert Panel on Population and Prevention Science of the American Heart Association Circulation, June 1, 2004; 109(21): 2655 - 2671. [Abstract] [Full Text] [PDF]
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 D. Campa, S. Zienolddiny, V. Maggini, V. Skaug, A. Haugen, and F. Canzian Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer Carcinogenesis, February 1, 2004; 25(2): 229 - 235. [Abstract] [Full Text] [PDF]
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A. Bhatnagar Cardiovascular pathophysiology of environmental pollutants Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H479 - H485. [Full Text] [PDF]
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C. A. Pope III, R. T. Burnett, G. D. Thurston, M. J. Thun, E. E. Calle, D. Krewski, and J. J. Godleski Cardiovascular Mortality and Long-Term Exposure to Particulate Air Pollution: Epidemiological Evidence of General Pathophysiological Pathways of Disease Circulation, January 6, 2004; 109(1): 71 - 77. [Abstract] [Full Text] [PDF]
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V. Mishra Indoor air pollution from biomass combustion and acute respiratory illness in preschool age children in Zimbabwe Int. J. Epidemiol., October 1, 2003; 32(5): 847 - 853. [Abstract] [Full Text] [PDF]
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 Y. Goto, J. C. Hogg, T. Suwa, K. B. Quinlan, and S. F. van Eeden A novel method to quantify the turnover and release of monocytes from the bone marrow using the thymidine analog 5'-bromo-2'-deoxyuridine Am J Physiol Cell Physiol, August 1, 2003; 285(2): C253 - C259. [Abstract] [Full Text] [PDF]
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A.G.N. Agusti, A. Noguera, J. Sauleda, E. Sala, J. Pons, and X. Busquets Systemic effects of chronic obstructive pulmonary disease Eur. Respir. J., February 1, 2003; 21(2): 347 - 360. [Abstract] [Full Text] [PDF]
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T. Fujii, J. C. Hogg, N. Keicho, R. Vincent, S. F. Van Eeden, and S. Hayashi Adenoviral E1A modulates inflammatory mediator expression by lung epithelial cells exposed to PM10 Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L290 - L297. [Abstract] [Full Text] [PDF]
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M. J. Tobin Compliance (COMmunicate PLease wIth Less Abbreviations, Noun Clusters, and Exclusiveness) Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): 1534 - 1536. [Full Text] [PDF]
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T. Fujii, S. Hayashi, J. C. Hogg, H. Mukae, T. Suwa, Y. Goto, R. Vincent, and S. F. van Eeden Interaction of Alveolar Macrophages and Airway Epithelial Cells Following Exposure to Particulate Matter Produces Mediators that Stimulate the Bone Marrow Am. J. Respir. Cell Mol. Biol., July 1, 2002; 27(1): 34 - 41. [Abstract] [Full Text] [PDF]
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 T. Suwa, J. C. Hogg, K. B. Quinlan, A. Ohgami, R. Vincent, and S. F. van Eeden Particulate air pollution induces progression of atherosclerosis J. Am. Coll. Cardiol., March 20, 2002; 39(6): 935 - 942. [Abstract] [Full Text] [PDF]
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M. J. TOBIN Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 642 - 662. [Full Text] [PDF]
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