A role for associated transition metals in the immunotoxicity of inhaled ambient particulate matter.

Zelikoff, Judith T.; Schermerhorn, Kimberly R; Fang, Kaijie; Cohen, Mitchell D.; Schlesinger, Richard B.

doi:10.1289/ehp.02110s5871

Cited by 73 publications

(40 citation statements)

References 36 publications

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“…These reports have been supported by studies in rodent models that provide evidence that PM can modulate pulmonary immune responses (47). The observed interactions between Ni and MALP-2 on the elaboration of chemokine release from HLF suggest that pulmonary immune responses in humans may also be altered as a consequence of PM exposure.…”

Section: Discussionmentioning

confidence: 77%

Nickel Alterations of TLR2-Dependent Chemokine Profiles in Lung Fibroblasts Are Mediated by COX-2

Brant¹,

Fabisiak²

2008

Am J Respir Cell Mol Biol

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Particulate matter air pollution (PM) has been linked with chronic respiratory diseases. Real-life exposures are likely to involve a mixture of chemical and microbial stimuli, yet little attention has been paid to the potential interactions between PM components (e.g., Ni) and microbial agents on the development of inflammatory-like conditions in the lung. Using the Toll-like receptor (TLR)-2 agonist MALP-2 as a lipopeptide relevant to microbial colonization, we hypothesized that nickel sensitizes human lung fibroblasts (HLF) for microbial-driven chemokine release through modulation of TLR signaling pathways. NiSO 4 (200 mM) synergistically enhanced CXCL8, yet antagonized CXCL10 mRNA expression and protein release from HLF in response to MALP-2. RT 2 -PCR pathway-focused array results indicated that NiSO 4 exposure did not alter the expression of TLRs or their downstream signaling mediators, yet significantly increased the expression of cyclooxygenase 2 (COX-2). Moreover, when NiSO 4 was given in combination with MALP-2, there was an amplified induction of COX-2 mRNA and protein along with its metabolic product, PGE2, in HLF. The COX-2 inhibitor, NS-398, attenuated NiSO 4 and MALP-2-induced PGE2 and CXCL8 release and partially reversed the NiSO 4 -dependent inhibition of MALP-2-induced CXCL10 release from HLF. These data indicate that NiSO 4 alters the pattern of TLR-2-dependent chemokine release from HLF via a COX-2-mediated pathway. The quantitative and qualitative effects of NiSO 4 on microbial-driven chemokine release from HLF shed new light on how PM-derived metals can exacerbate respiratory diseases.Keywords: COX-2; nickel; inflammation; chemokines; fibroblasts Particulate matter air pollution (PM) is a contributing risk factor for many adverse health effects, including respiratory diseases (1). Real-life scenarios are likely to involve exposures not only to chemical stresses such as PM, but microbial stimuli as well. While much attention has been paid to microbial-driven inflammation in the lung, limited information is available regarding the potential interactions between PM exposures and microbial stress on respiratory function. There are reports, however, of increased numbers of hospitalizations for respiratory disorders including infections on days of increased levels of PM (2). In support of these epidemiologic findings, several rodent models have shown PM exposure can increase susceptibility to infectious bacteria such as Listeria monocytogenes and Streptococcus pneumoniae (3, 4).Recent evidence suggests that colonization with species originally considered commensal and not causing overt disease (e.g., Mycoplasma fermentans) also has the potential to interact with other stimuli and/or alter biological responses in infected host cells (5, 6). For example, we have previously shown that exposure of human lung fibroblast cells (HLF) to M. fermentans synergistically enhances the release of IL-6 by PM in the form of residual oil fly ash (ROFA) compared to either stimulus alone (7). It is well recognized t...

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Section: Discussionmentioning

confidence: 77%

Nickel Alterations of TLR2-Dependent Chemokine Profiles in Lung Fibroblasts Are Mediated by COX-2

Brant¹,

Fabisiak²

2008

Am J Respir Cell Mol Biol

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“…Recent animal studies suggest that PM or its constituents play a role in affecting host defenses and increase susceptibility to pulmonary infections. [411][412][413] Hypoxemia Another mechanistic pathway involves PM-induced lung damage (potentially including oxidative lung damage and inflammation), declines in lung function, respiratory distress, and hypoxemia. In the case report discussed above, 332 exposure to high levels of aerosolized oil fly ash particles eventually led to the experiencing of hypoxic respiratory failure.…”

Section: Modulated Host Defenses and Immunitymentioning

confidence: 99%

Health Effects of Fine Particulate Air Pollution: Lines that Connect

Pope

Dockery²

2006

Journal of the Air & Waste Management Association

5,499

3,159

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Efforts to understand and mitigate the health effects of particulate matter (PM) air pollution have a rich and interesting history. This review focuses on six substantial lines of research that have been pursued since 1997 that have helped elucidate our understanding about the effects of PM on human health. There has been substantial progress in the evaluation of PM health effects at different time-scales of exposure and in the exploration of the shape of the concentration-response function. There has also been emerging evidence of PM-related cardiovascular health effects and growing knowledge regarding interconnected general pathophysiological pathways that link PM exposure with cardiopulmonary morbidity and mortality. Despite important gaps in scientific knowledge and continued reasons for some skepticism, a comprehensive evaluation of the research findings provides persuasive evidence that exposure to fine particulate air pollution has adverse effects on cardiopulmonary health. Although much of this research has been motivated by environmental public health policy, these results have important scientific, medical, and public health implications that are broader than debates over legally mandated air quality standards.

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Section: Coarse Particles and Respiratory Infections In Childrenmentioning

confidence: 99%

“…33 Particulate matter is likely immunosuppressive and may undermine normal pulmonary antimicrobial defense mechanisms. 34 Additional studies are needed to explore the potential mechanisms.In our study, some gaseous pollutants showed significant effects on hospitalization for respiratory infections, but the influences were no longer significant when particulate matter was taken into consideration. The only exception is the effect of NO 2 in girls, which remained significant even after controlling for particulate matter.…”

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confidence: 99%

Coarse Particulate Matter and Hospitalization for Respiratory Infections in Children Younger Than 15 Years in Toronto: A Case-Crossover Analysis

2005

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ABSTRACT. Objectives. The purpose of this study was to examine the association between ambient air pollution and hospitalization for respiratory infections among children who were younger than 15 years in Toronto during a 4-year period (1998 -2001).Methods. Exposures averaged during periods that varied from 1 to 7 days were used to assess the effects of air pollutants, including thoracic particulate matter (PM 10 ), fine (PM 2.5 ) and coarse (PM 10 -2.5 ) particulate matter, carbon monoxide (CO), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ), on hospitalization for respiratory infections. A case-crossover design was used to calculate odds ratios for the hospitalization adjusted for daily weather conditions with an incremented exposure corresponding to the interquartile range in air pollution exposures.Results. When particulate matter and gaseous pollutants were mutually taken into account, the effect remained pronounced for PM 10 -2.5 in both boys and girls. The adjusted odds ratio for 6-day average exposure to PM 10 -2.5 with an increment of 6.5 g/m 3 was 1.15 (95% confidence interval: 1.02-1.30) for boys and 1.18 (95% confidence interval: 1.01-1.36) for girls. The effect also remained for PM 10 in boys and for NO 2 in girls. PM 2.5 , CO, SO 2 , and O 3 showed no significant effects on hospitalization for respiratory infection in both genders when other pollutants were taken into consideration.Conclusion. Our study suggested a detrimental effect of relatively low levels of ambient particulate matter and gaseous pollutants, especially coarse particulate matter and NO 2 , on hospitalization for respiratory infections in children. Pediatrics 2005;116:e235-e240. URL: www. pediatrics.org/cgi/doi/10.1542/peds.2004-2012; air pollution, coarse particulate matter, gaseous pollutants, hospitalization for respiratory infection, case-crossover analysis, risk assessment.ABBREVIATIONS. CO, carbon monoxide; SO 2 , sulfur dioxide; NO 2 , nitrogen dioxide; O 3 , ozone; PM 10 , thoracic particulate matter Ͻ10 m in aerodynamic diameter; PM 2.5 , fine particulate matter Ͻ2.5 m in aerodynamic diameter; TEOM, tapered element oscillating microbalance; PM 10 -2.5 , coarse particulate matter between 2.5 and 10 m in aerodynamic diameter; OR, odds ratio; CI, confidence interval; TSP, total suspended particles. L ower respiratory infection is a main cause of mortality and morbidity in children in developing countries. Morbidity from childhood respiratory infections is also high in developed countries. 1 Although respiratory infections in children are usually nonfatal in developed countries, they heavily burden the health care systems. 2 Additional progress in preventing the diseases will have a significant impact on children's health. 1 Although there is abundant evidence linking outdoor air pollution with respiratory symptoms, reduced lung function, bronchial reactivity, and asthma, the relationship of hospital morbidity for respiratory infections to a relatively low level of exposure to air pollution in children has...

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A role for associated transition metals in the immunotoxicity of inhaled ambient particulate matter.

Cited by 73 publications

References 36 publications

Nickel Alterations of TLR2-Dependent Chemokine Profiles in Lung Fibroblasts Are Mediated by COX-2

Nickel Alterations of TLR2-Dependent Chemokine Profiles in Lung Fibroblasts Are Mediated by COX-2

Health Effects of Fine Particulate Air Pollution: Lines that Connect

Coarse Particulate Matter and Hospitalization for Respiratory Infections in Children Younger Than 15 Years in Toronto: A Case-Crossover Analysis

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