Clara cells drive eosinophil accumulation in allergic asthma

Sonar, Sanchaita Sriwal; Ehmke, M.; Marsh, Leigh M.; Dietze, Jared L.; Dudda, Jan C.; Conrad, Melanie L.; Renz, H.; Nockher, Wolfgang Andreas

doi:10.1183/09031936.00197810

Cited by 24 publications

(27 citation statements)

References 40 publications

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“…CC-16 is a natural immune-regulator protecting the respiratory tract from unwanted inflammatory reactions [78]. CC-16 levels in serum increase when lung epithelium permeability is adversely affected by air pollutants or other lung toxicants.…”

Section: Discussionmentioning

confidence: 99%

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India

et al. 2013

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BackgroundWe assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status.MethodsIndoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed.ResultsPM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group.ConclusionsPhotocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India

et al. 2013

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“…13,14 Furthermore, CC also respond actively to Th2-inflammation by producing eotaxin and undergoing epidermal growth factor receptor (EGFR)-mediated mucus metaplasia. [15][16][17] Related to this, our previous findings indicated that CC mucous metaplasia leads to a marked decrease in CCSP and SP-D secretion. 18,19 In common with epithelial cells, AM are also plastic cells involved in the first line of defense against inhaled agents, which are endowed with a high phagocytic and microbicidal potential and a lower expression of MHC class II molecules.…”

Section: Introductionmentioning

confidence: 92%

Protective phenotypes of club cells and alveolar macrophages are favored as part of endotoxin-mediated prevention of asthma

García

Leimgruber

Echevarría

et al. 2014

Exp Biol Med (Maywood)

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Atopic asthma is a chronic allergic disease that involves T-helper type 2 (Th2)-inflammation and airway remodeling. Bronchiolar club cells (CC) and alveolar macrophages (AM) are sentinel cells of airway barrier against inhaled injuries, where allergy induces mucous metaplasia of CC and the alternative activation of AM, which compromise host defense mechanisms and amplify Th2-inflammation. As there is evidence that high levels of environmental endotoxin modulates asthma, the goal of this study was to evaluate if the activation of local host defenses by Lipopolysaccharide (LPS) previous to allergy development can contribute to preserving CC and AM protective phenotypes. Endotoxin stimulus before allergen exposition reduced hallmarks of allergic inflammation including eosinophil influx, Interleukin-4 and airway hyperreactivity, while the T-helper type 1 related cytokines IL-12 and Interferon-γ were enhanced. This response was accompanied by the preservation of the normal CC phenotype and the anti-allergic proteins Club Cell Secretory Protein (CCSP) and Surfactant-D, thereby leading to lower levels of CC metaplasia and preventing the increase of the pro-Th2 cytokine Thymic stromal lymphopoietin. In addition, classically activated alveolar macrophages expressing nitric oxide were promoted over the alternatively activated ones that expressed arginase-1. We verified that LPS induced a long-term overexpression of CCSP and the innate immune markers Toll-like receptor 4, and Tumor Necrosis Factor-α, changes that were preserved in spite of the allergen challenge. These results demonstrate that LPS pre-exposition modifies the local bronchioalveolar microenvironment by inducing natural anti-allergic mechanisms while reducing local factors that drive Th2 type responses, thus modulating allergic inflammation.

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“…As a consequence of exposure to the antigen, the release of eosinophils from bone marrow is mainly influenced by interleukin (IL)-5 and specific chemoattractants, such as eotaxin (Brightling, 2001). Recent investigation revealed Clara cells, important part of the “immunomodulatory barrier” of the airway epithelium, as the principal source of eotaxin in the lung (Sonar et al, 2012). It is also believed that exposure to the antigen induces trafficking of IL-5-producing T lymphocytes to the bone marrow, further promoting eosinophilopoiesis through IL-5 signaling (Gauvreau et al, 2009).…”

Section: Immune Responsementioning

confidence: 99%

Eosinophilic Inflammation in Allergic Asthma

et al. 2013

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Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL)-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR)3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modulation of immune response, induction of airway hyperresponsiveness and remodeling, characteristic features of asthma. Various types of promising treatments for reducing asthmatic response are related to reduction in eosinophil counts both in human and experimental models of pulmonary allergic inflammation, showing that the recruitment of these cells really plays an important role in the pathophysiology of allergic diseases such asthma.

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Clara cells drive eosinophil accumulation in allergic asthma

Cited by 24 publications

References 40 publications

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India

Protective phenotypes of club cells and alveolar macrophages are favored as part of endotoxin-mediated prevention of asthma

Eosinophilic Inflammation in Allergic Asthma

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