Residual Oil Fly Ash Amplifies Allergic Cytokines, Airway Responsiveness, and Inflammation in Mice

Gavett, Stephen H.; Madison, Sharon L.; Stevens, M. Allen; Costa, Daniel L.

doi:10.1164/ajrccm.160.6.9901053

Cited by 66 publications

(49 citation statements)

References 26 publications

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“…These challenges are not antigenic in nature but rather behave as irritants in provoking inflammation and/or bronchoconstriction. Similar effects have been seen in allergic animals exposed to ROFA as illustrated here and in previous reports (27,28). This general increase in airway responsiveness and lung injury through dual exposure to allergen and PM may be an additive effect of two proinflammatory stimuli, although synergistic relationships in which both stimuli are required to elicit a pulmonary response are also possible.…”

Section: Discussionsupporting

confidence: 88%

Air pollutant-enhanced respiratory disease in experimental animals.

Gilmour

Daniels

McCrillis

et al. 2001

Environ Health Perspect

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Studies in animals have shown that a wide range of airborne particulates including cigarette smoke, acid aerosols, metals, organic compounds, and combustion products can interfere with the normal defense processes of the lung to enhance susceptibility to respiratory infection or exacerbate allergic diseases. Such detrimental effects are less easy to quantify in humans because of the difficulties in obtaining comprehensive exposure history and health status in large populations and because of the inherent dangers of inducing disease in clinical studies. In this article we describe examples of how air pollutants affect lung disease in experimental animal systems. This information can be used to predict the health risk of simple and complex exposures and to lend insight into the mechanisms of air pollution toxicity.

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Section: Discussionsupporting

confidence: 88%

Air pollutant-enhanced respiratory disease in experimental animals.

Gilmour

Daniels

McCrillis

et al. 2001

Environ Health Perspect

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“…Pulmonary responsiveness to bronchoconstrictor agents was determined by measuring airway pressure and flow in anesthetized, ventilated Aqp5 ϩ/ϩ and Aqp5 Ϫ/Ϫ mice (n ϭ 6 each group) according to a published method (17). Briefly, anesthetized mice were tracheostomized by using a custom built cannula with ports for inspiration and expiration, and for monitoring airway pressure and airway flow.…”

Section: Methodsmentioning

confidence: 99%

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Krane

Fortner

Hand

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

105

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Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveolar type II cells, and in tracheal and bronchial epithelium. Aqp5 knockout (Aqp5 ؊/؊ ) mice were used to analyze AQP5 function in pulmonary physiology. Compared with Aqp5 ؉/؉ mice, Aqp5 ؊/؊ mice show a significantly increased concentration-dependent bronchoconstriction to intravenously administered Ach, as shown by an increase in total lung resistance and a decrease in dynamic lung compliance (P < 0.05). Likewise, Penh, a measure of bronchoconstriction, was significantly enhanced in Aqp5 ؊/؊ mice challenged with aerosolized methacholine (P < 0.05). The hyperreactivity to bronchoconstriction observed in the Aqp5 ؊/؊ mice was not due to differences in tracheal smooth muscle contractility in isolated preparations or to altered levels of surfactant protein B. These data suggest a novel pathway by which AQP5 influences bronchoconstriction. This observation is of special interest because studies to identify genetic loci involved in airway hyperresponsiveness associated with asthma bracket genetic intervals on human chromosome 12q and mouse chromosome 15, which contain the Aqp5 gene.A quaporin 5 (AQP5) is a mercury-sensitive water channel expressed in mouse salivary gland acinar cells, alveolar type I cells, lacrimal glands, and the eye (1-3). However, the function of AQP5 in mouse lung physiology and pathophysiology is largely unknown. Recent studies have explored the regulation of Aqp5 gene expression in normal and disease states. In a mouse model of acute lung injury, AQP5 mRNA and protein expression were significantly decreased in association with pulmonary inflammation and edema resulting from adenoviral infection (4). Moreover, AQP5 expression in a murine lung epithelial cell line (MLE-12) is modulated by the proinf lammatory cytokine TNF-␣ through an nuclear factor (NF)-B-dependent pathway (5). Keratinocyte growth factor also has been shown to mediate the differentiation status of alveolar epithelial cells and AQP5 expression (6). However, a clear understanding of AQP5 function in the lung remains to be discerned.Previously published studies have addressed functional questions limited to the examination of the role of AQP5 in type I cells in fluid clearance and airspace-capillary osmotic water permeability. Of significance, isolated perfused lungs from Aqp5 Ϫ/Ϫ mice were shown to have a 10-fold reduction in airspace-capillary osmotic water permeability (7). Experiments addressing the role of AQP5 in alveolar fluid clearance failed to indicate a role for AQP5 in this process under certain physiological conditions (8). Based on the results of these studies, some have concluded that AQP5 does not play a major role in lung physiology. Contrary to these conclusions, the data reported here clearly define a...

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“…The metal composition of the ash appears critical to the development of airway hyperreactivity, as assessed by acetylcholine challenge (9). In addition, there are effects of ROFA on sensitization to allergens in animal models of pulmonary allergy, with significant elevations in eosinophils, IL-10, antigen specific immunoglobulin E, and associated immediate bronchoconstriction responses to antigen challenge (36)(37)(38)(39). This effect can be reproduced by the metal leachate of ROFA as well as individual metallic constituents of ROFA (35) and can be abrogated by DMTU pretreatment (40).…”

Section: Physiologic Biochemical Cellular and Molecular Effects Ofmentioning

confidence: 99%

Biologic effects of oil fly ash.

Ghio

Silbajoris

Carson

et al. 2002

Environ Health Perspect

176

104

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Epidemiologic studies have demonstrated increased human morbidity and mortality with elevations in the concentration of ambient air particulate matter (PM). Fugitive fly ash from the combustion of oil and residual fuel oil significantly contributes to the ambient air particle burden. Residual oil fly ash (ROFA) is remarkable in the capacity to provoke injury in experimental systems. The unique composition of this emission source particle makes it particularly useful as a surrogate for ambient air PM in studies of biologic effects testing the hypothesis that metals mediate the biologic effects of air pollution particles. A majority of the in vitro and animal model investigations support the postulate that transition metals present in ROFA (especially vanadium) participate in Fenton-like chemical reactions to produce reactive oxygen species. This is associated with tyrosine phosphorylation, nuclear factor kappa B and other transcription factor activation, induction of inflammatory mediator expression, and inflammatory lung injury. It is also evident that vanadium accounts for a significant portion of the biologic activity of ROFA. The extrapolation of this body of investigation on ROFA to the field of ambient air PM is difficult, as particles in numerous environments have such small amounts of vanadium.

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Residual Oil Fly Ash Amplifies Allergic Cytokines, Airway Responsiveness, and Inflammation in Mice

Cited by 66 publications

References 26 publications

Air pollutant-enhanced respiratory disease in experimental animals.

Air pollutant-enhanced respiratory disease in experimental animals.

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

Biologic effects of oil fly ash.

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