Exposure of Adult Mice to Environmental Tobacco Smoke Fails to Enhance the Immune Response to Inhaled Antigen

Bowles, Kimberly S.; Horohov, David W.; Paulsen, Daniel B.; LeBlanc, Casey J.; Littlefield-Chabaud, Martha A.; Ahlert, Terry; Ahlert, Ken; Pourciau, Susan; Penn, Arthur

doi:10.1080/08958370590885690

Cited by 19 publications

(13 citation statements)

References 52 publications

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“…Although several prior studies examining ETS exposure in combination with allergen exposure in mice have demonstrated enhanced Th2 responses (17, 18, 28 -30), other studies have demonstrated that the combination of ETS exposure and OVA allergen can inhibit Th2 responses and AHR (31)(32)(33). The differences in the results in these studies may be due to differences in ETS and OVA exposure protocols, differences in exposure to mainstream smoke vs ETS, as well as differences in timing of ETS exposure during the sensitization compared with the allergen challenge period.…”

Section: Discussionmentioning

confidence: 99%

Coexposure to Environmental Tobacco Smoke Increases Levels of Allergen-Induced Airway Remodeling in Mice

Min

Song

Miller

et al. 2007

The Journal of Immunology

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Environmental tobacco smoke (ETS) can increase asthma symptoms and the frequency of asthma attacks. However, the contribution of ETS to airway remodeling in asthma is at present unknown. In this study, we have used a mouse model of allergen-induced airway remodeling to determine whether the combination of chronic exposure to ETS and chronic exposure to OVA allergen induces greater levels of airway remodeling than exposure to either chronic ETS or chronic OVA allergen alone. Mice exposed to chronic ETS alone did not develop significant eosinophilic airway inflammation, airway remodeling, or increased airway hyperreactivity to methacholine. In contrast, mice exposed to chronic OVA allergen had significantly increased levels of peribronchial fibrosis, increased thickening of the smooth muscle layer, increased mucus, and increased airway hyperreactivity which was significantly enhanced by coexposure to the combination of chronic ETS and chronic OVA allergen. Mice coexposed to chronic ETS and chronic OVA allergen had significantly increased levels of eotaxin-1 expression in airway epithelium which was associated with increased numbers of peribronchial eosinophils, as well as increased numbers of peribronchial cells expressing TGF-β1. These studies suggest that chronic coexposure to ETS significantly increases levels of allergen-induced airway remodeling (in particular smooth muscle thickness) and airway responsiveness by up-regulating expression of chemokines such as eotaxin-1 in airway epithelium with resultant recruitment of cells expressing TGF-β1 to the airway and enhanced airway remodeling.

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Section: Discussionmentioning

confidence: 99%

Coexposure to Environmental Tobacco Smoke Increases Levels of Allergen-Induced Airway Remodeling in Mice

Min

Song

Miller

et al. 2007

The Journal of Immunology

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“…For smoke inhalation, sidestream smoke comprised approximately 90% of SHS, and the remaining 10% consisted of exhaled mainstream smoke (32)(33)(34). Here, sidestream smoke served as a surrogate for SHS (32)(33)(34).…”

Section: Shs Exposurementioning

confidence: 99%

Role of CXCL5 in Leukocyte Recruitment to the Lungs during Secondhand Smoke Exposure

Balamayooran¹,

Batra²,

Cai³

et al. 2012

Am J Respir Cell Mol Biol

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Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality in the United States. The major cause of COPD is cigarette smoking. Extensive leukocyte influx into the lungs, mediated by chemokines, is a critical event leading to COPD. Although both resident and myeloid cells secrete chemokines in response to inflammatory stimuli, little is known about the role of epithelial-derived chemokines, such as CXC chemokine ligand (CXCL)5, in the pathogenesis of cigarette smoke-induced inflammation. To explore the role of CXCL5, we generated CXCL5 genedeficient mice and exposed them to secondhand smoke (SHS) for 5 hours/day for 5 days/week up to 3 weeks (subacute exposure). We observed a reduced recruitment of leukocytes to the lungs of CXCL5 2/2 mice compared with their wild-type (WT) counterparts, and noted that macrophages comprised the predominant leukocytes recruited to the lungs. Irradiation experiments performed on CXCL5 2/2 or WT mice transplanted with WT or CXCL5 2/2 bone marrow revealed that resident but not hematopoietic cell-driven CXCL5 is important for mediating SHS-induced lung inflammation. Interestingly, we observed a significant reduction of monocyte chemotactic protein-1 (MCP-1/CC chemokine ligand 2) concentrations in the lungs of CXCL5 2/2 mice. The instillation of recombinant MCP-1 in CXCL52/2 mice reversed macrophage recruitment. Our results also show the reduced activation of NF-kB/p65 in the lungs, as well as the attenuated activation of C-Jun N-terminal kinase, p42/44, and p38 mitogen-activated protein kinases and the expression of intercellular adhesion molecule-1 in the lungs of SHS-exposed CXCL5 2/2 mice. Our findings suggest an important role for CXCL5 in augmenting leukocyte recruitment in SHS-induced lung inflammation, and provide novel insights into CXCL5-driven pathogenesis.Keywords: smoke; CXCL5/LIX; macrophages; chemokines; cytokines Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States (1-3). According to recent reports, the prevalence of COPD in the United States involves more than 12 million, with an annual mortality of 120,000 (1-3). COPD is an irreversible disease characterized by airway inflammation (chronic bronchitis) and airspace enlargement, along with the destruction of lung parenchyma (emphysema) (4, 5). Although the molecular and cellular mechanisms that contribute to the development of COPD are not well understood, substantial recruitment and activation of inflammatory cells into the airspaces and lung parenchyma has been documented in humans with COPD and implicated in its pathogenesis (4, 5).Cigarette smoking accounts for most of the debilitating effects of COPD, but other environmental risk factors include air pollution and chronic occupational exposure to various dusts (6). Why only a small proportion (10-20%) of smokers develops COPD remains unclear (7). Cigarette smoke (CS) contains more than 4,700 chemicals (8), and is a powerful inducer of inflammatory mediators, including oxidants and proteases,...

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“…However, not all studies supported a positive contribution of cigarette smoke exposure to the allergic phenotype and sensitization phenomenon, possibly as a result from the variable experimental conditions used among different laboratories (e.g., the use of environmental vs mainstream smoke, whole-body vs nose-only exposure, etc.) (11,12,14,15). One outstanding observation was that the effects of smoke exposure on allergic responses appear to be dose dependent (15).…”

mentioning

confidence: 99%

Concomitant Inhalation of Cigarette Smoke and Aerosolized Protein Activates Airway Dendritic Cells and Induces Allergic Airway Inflammation in a TLR-Independent Way

Robays

Lanckacker

Moerloose

et al. 2009

The Journal of Immunology

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Cigarette smoking is associated with the development of allergic asthma. In mice, exposure to cigarette smoke sensitizes the airways toward coinhaled OVA, leading to OVA-specific allergic inflammation. Pulmonary dendritic cells (DCs) are professional APCs involved in immunosurveillance and implicated in the induction of allergic responses in lung. We investigated the effects of smoking on some of the key features of pulmonary DC biology, including trafficking dynamics and cellular activation status in different lung compartments. We found that cigarette smoke inhalation greatly amplified DC-mediated transport of inhaled Ags to mediastinal lymph nodes, a finding supported by the up-regulation of CCR7 on airway DCs. Pulmonary plasmacytoid DCs, which have been involved in inhalational tolerance, were reduced in number after smoke exposure. In addition, combined exposure to cigarette smoke and OVA aerosol increased surface expression of MHC class II, CD86, and PDL2 on airway DCs, while ICOSL was strongly down-regulated. Although inhaled endotoxins, which are also present in cigarette smoke, have been shown to act as DC activators and Th2-skewing sensitizers, TLR4-deficient and MyD88 knockout mice did not show impaired eosinophilic airway inflammation after concomitant exposure to cigarette smoke and OVA. From these data, we conclude that cigarette smoke activates the pulmonary DC network in a pattern that favors allergic airway sensitization toward coinhaled inert protein. The TLR independency of this phenomenon suggests that alternative immunological adjuvants are present in cigarette smoke.

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Exposure of Adult Mice to Environmental Tobacco Smoke Fails to Enhance the Immune Response to Inhaled Antigen

Cited by 19 publications

References 52 publications

Coexposure to Environmental Tobacco Smoke Increases Levels of Allergen-Induced Airway Remodeling in Mice

Coexposure to Environmental Tobacco Smoke Increases Levels of Allergen-Induced Airway Remodeling in Mice

Role of CXCL5 in Leukocyte Recruitment to the Lungs during Secondhand Smoke Exposure

Concomitant Inhalation of Cigarette Smoke and Aerosolized Protein Activates Airway Dendritic Cells and Induces Allergic Airway Inflammation in a TLR-Independent Way

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