Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys

Schelegle, Edward S.; Miller, Lisa; Gershwin, Laurel J.; Fanucchi, Michelle V.; Winkle, Laura S. Van; Gerriets, Joan E.; Walby, William F.; Mitchell, Valerie L.; Tarkington, Brian K.; Wong, Viviana; Baker, Gregory L.; Pantle, L. M.; Joad, Jesse P.; Pinkerton, Kent E.; Wu, Reen; Evans, Michael J.; Hyde, Dallas M.; Plopper, Charles G.

doi:10.1016/s0041-008x(03)00218-7

Cited by 91 publications

(119 citation statements)

References 27 publications

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“…Previous research has shown a synergistic effect of O 3 1 HDMA exposure, with O 3 amplifying the allergic, structural, and neural remodeling effects of HDMA sensitization and inhalation (10,14,25). Also, previous work has shown that immediately after 6 months of exposure to HDMA, O 3 , or O 3 1 HDMA, similar 5-HT-induced increases in neurally mediated ASM contractions were seen in all the groups (18).…”

Section: Direct Effect Of 5-ht On Asm Tensionmentioning

confidence: 81%

“…Although the mechanisms responsible for asthma symptoms are debatable, research shows that O 3 and HDMA exposure leads to functional, structural, neural, vascular, and immunological alterations in airways (10)(11)(12)(13)(14)(15)(16). This airway remodeling indicates that environmental insults early in life can have life-long deleterious effects on lung function and may lead to chronic asthma symptoms.…”

Section: Clinical Relevancementioning

confidence: 99%

“…Patients with asthma have higher 5-HT plasma levels, which are inversely correlated with lung function, and drug treatments that lower plasma 5-HT decrease symptom severity and improve lung function (6,28,29). Our lab has shown that exposure of O 3 1 HDMA induces AHR and exacerbates 5-HT-mediated airway smooth muscle (ASM) contraction in a model of childhood asthma (18) and that the combined exposure of O 3 1 HDMA results in alterations in 9 of 10 immune, structural, and functional end points, with six of the end points demonstrating greater than additive effects of O 3 or HDMA exposure alone (10). Studies have epidemiologically confirmed asthma persistence from childhood through adulthood, linking persistent symptoms to atopy, smoking, air pollution (including O 3 ), early age at onset of asthma, and airway remodeling (30)(31)(32)(33)(34).…”

Section: Clinical Relevancementioning

confidence: 99%

“…All animals were sensitized to HDMA and exposed to 11 episodes of FA or O 3 1 HDMA as previously described (10,18) (Figure 1 …”

Section: General Protocolmentioning

confidence: 99%

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Persistence of Serotonergic Enhancement of Airway Response in a Model of Childhood Asthma

Moore

Hyde

Miller

et al. 2014

Am J Respir Cell Mol Biol

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The persistence of airway hyperresponsiveness (AHR) and serotonergic enhancement of airway smooth muscle (ASM) contraction induced by ozone (O 3 ) plus allergen has not been evaluated. If this mechanism persists after a prolonged recovery, it would indicate that early-life exposure to O 3 plus allergen induces functional changes predisposing allergic individuals to asthmarelated symptoms throughout life, even in the absence of environmental insult. A persistent serotonergic mechanism in asthma exacerbations may offer a novel therapeutic target, widening treatment options for patients with asthma. The objective of this study was to determine if previously documented AHR and serotonin-enhanced ASM contraction in allergic monkeys exposed to O 3 plus house dust mite allergen (HDMA) persist after prolonged recovery. Infant rhesus monkeys sensitized to HDMA were exposed to filtered air (FA) (n = 6) or HDMA plus O 3 (n = 6) for 5 months. Monkeys were then housed in a FA environment for 30 months. At 3 years, airway responsiveness was assessed. Airway rings were then harvested, and ASM contraction was evaluated using electrical field stimulation with and without exogenous serotonin and serotoninsubtype receptor antagonists. Animals exposed to O 3 plus HDMA exhibited persistent AHR. Serotonin exacerbated the ASM contraction in the exposure group but not in the FA group.Serotonin subtype receptors 2, 3, and 4 appear to drive the response. Our study shows that AHR and serotonin-dependent exacerbation of cholinergic-mediated ASM contraction induced by early-life exposure to O 3 plus allergen persist for at least 2.5 years and may contribute to a persistent asthma phenotype.

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Section: Direct Effect Of 5-ht On Asm Tensionmentioning

confidence: 81%

Section: Clinical Relevancementioning

confidence: 99%

Section: Clinical Relevancementioning

confidence: 99%

“…All animals were sensitized to HDMA and exposed to 11 episodes of FA or O 3 1 HDMA as previously described (10,18) (Figure 1 …”

Section: General Protocolmentioning

confidence: 99%

See 2 more Smart Citations

Persistence of Serotonergic Enhancement of Airway Response in a Model of Childhood Asthma

Moore

Hyde

Miller

et al. 2014

Am J Respir Cell Mol Biol

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“…Ozone exposure was also shown to cause an enhanced response to inhaled allergens, both in normal volunteers and in patients with allergic asthma (9)(10)(11). Animal models of allergic asthma have been used to study the complex interaction between ozone and allergen (12)(13)(14).…”

mentioning

confidence: 99%

Ozone Enhances Pulmonary Innate Immune Response to a Toll-Like Receptor–2 Agonist

Oakes

O’Connor

Warg

et al. 2013

Am J Respir Cell Mol Biol

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Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases Toll-like receptor-4 (TLR4)-mediated responses to subsequent stimulation with LPS. To explore the pulmonary innate immune response to ozone exposure further, we investigated the effects of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Whole-lung lavage (WLL) and lung tissue were harvested from C57BL/6 mice after exposure to ozone or filtered air, followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the WLL, the surface expression of TLRs on macrophages, and lung RNA genomic expression profiles were examined. We demonstrated an increased WLL cell influx, increased IL-6 and chemokine KC (Cxcl1), and decreased macrophage inflammatory protein (MIP)-1a and TNF-a in response to Pam3CYS as a result of ozone pre-exposure. We also observed the increased cell surface expression of TLR4, TLR2, and TLR1 on macrophages as a result of ozone alone or in combination with Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase in the expression of genes related to injury repair and the cell cycle as a result of ozone alone or in combination with Pam3CYS. Our results extend previous findings with ozone/LPS to other TLR ligands, and suggest that the ozone priming of innate immunity is a general mechanism. Gene expression profiling of lung tissue identified transcriptional networks and genes that contribute to the priming of innate immunity at the molecular level.

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Air Pollution

Reinhart¹,

White²,

Kim³

et al. 2011

Patty's Industrial Hygiene

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The present article summarizes about the air pollution and several legislations for its monitoring and control. Air pollution is a combination of both anthropogenic and natural origins and during the height of the industrial revolution that the health effects of air pollution in the cities became apparent. The first federal legislation involving air pollution was the Air Pollution Control Act of 1955 and provided funds for federal research on air pollution and followed by the Clean Air Act of 1963, which established a program within the U.S. Public Health Service for research on air pollution monitoring and control techniques. Later, the Air Quality Act of 1967 expanded the federal government's role involving air pollution by enacting enforcement procedures concerning interstate transport of pollutants. The Clean Air Act of 1970 brought about a number of significant changes and also undergone two amendments. The trends of the level and health effects of various chemical pollutants have been presented.

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Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys

Cited by 91 publications

References 27 publications

Persistence of Serotonergic Enhancement of Airway Response in a Model of Childhood Asthma

Persistence of Serotonergic Enhancement of Airway Response in a Model of Childhood Asthma

Ozone Enhances Pulmonary Innate Immune Response to a Toll-Like Receptor–2 Agonist

Air Pollution

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