Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-? Pathway.

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Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-? Pathway.

PLoS One. 2012;7(10):e47971

Authors: Kim JY, Sohn JH, Choi JM, Lee JH, Hong CS, Lee JS, Park JW

Abstract
The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-?. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-? production by alveolar macrophages through the PAR-2 pathway and whether the TNF-? production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-? production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-?. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-? production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-? blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-? level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-? dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.

PMID: 23094102 [PubMed – in process]

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Fractionated breath condensate sampling: H2O2 concentrations of the alveolar … – 7thSpace Interactive (press release)

Fractionated breath condensate sampling: H2O2 concentrations of the alveolar
7thSpace Interactive (press release)
Asthma is a chronic inflammatory disease of the airways but recent studies have shown that alveoli are also subject to pathophysiological changes. This study was undertaken to compare hydrogen peroxide (H2O2) concentrations in different parts of the

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Relation of bronchial and alveolar nitric oxide to exercise-induced bronchoconstriction in atopic children and adolescents.

Relation of bronchial and alveolar nitric oxide to exercise-induced bronchoconstriction in atopic children and adolescents.

Pediatr Allergy Immunol. 2011 Dec 7;

Authors: Linkosalo L, Lehtimäki L, Holm K, Kaila M, Moilanen E

Abstract
To cite this article: Linkosalo L, Lehtimäki L, Holm K, Kaila M, Moilanen E. Relation of bronchial and alveolar nitric oxide to exercise-induced bronchoconstriction in atopic children and adolescents. Pediatr Allergy Immunol 2011; Doi: 10.1111/j.1399-3038.2011.01223.x ABSTRACT: Background and objective:? Exercise challenge test is widely used in diagnostics and follow-up of childhood asthma, but the method is complex, time consuming, and expensive. In this study, we aimed to find out whether flow-independent nitric oxide (NO) parameters (bronchial NO flux [J’aw(NO) ] and alveolar NO concentration [CA(NO) ]) predict exercise-induced bronchoconstriction (EIB) in atopic children and adolescents with asthma-like symptoms. Also, the respective NO parameters corrected for axial backward diffusion (J’aw(NO) [TMAD] and CA(NO) [TMAD]) were calculated and included in the analysis. Methods:? Thirty patients (6-19?yr old) with confirmed atopy (positive skin prick tests or allergen-specific IgE) and asthma-like respiratory symptoms were included in the study. Before the current investigations, none of the patients had been diagnosed to have asthma and none were on inhaled corticosteroids. Exhaled NO was measured at multiple exhalation flow rates, and exercise challenge test was carried out. Bronchial NO flux and alveolar NO concentration were calculated according to the linear method with and without correction for axial backward diffusion. Sixty-six healthy school children served as controls. Results:? The patients were divided into two groups according to EIB. Patients with EIB (EIB+ group, n = 18) had enhanced bronchial NO output as compared to patients without EIB (EIB- group, n = 12); but the EIB- group did not differ from healthy controls. EIB+ group had also higher alveolar NO concentration than EIB- group and healthy controls, but EIB- group did not differ from healthy controls. When bronchial NO flux and alveolar NO concentration were corrected for axial diffusion, J’aw(NO) (TMAD) had equal difference as J’aw(NO) between the groups as expected. However, only EIB+ had higher CA(NO) (TMAD) than healthy controls, and the patient groups did not differ from each other. In patients, bronchial NO output correlated with the magnitude of exercise-induced change in PEF (r(s) = -0.388, p = 0.034), FEV(1) (r(s) = -0.395, p = 0.031), and FEF(50%) (r(s) = -0.431, p = 0.020), i.e., the higher the bronchial NO output, the larger the decrease in PEF/FEV(1) /FEF(50%) . Alveolar NO concentrations correlated with the change in FEV(1) (r(s) = -0.439, p = 0.015), FEF(50%) (r(s) = -0.454, p = 0.013), FEF(75%) (r(s) = -0.447, p?=?0.017), and FVC (r(s) ?=?-0.375, p?=?0.045). For J’aw(NO) (TMAD), the correlations and p-values were equal to those of J’aw(NO) , but, interestingly, CA(NO) (TMAD) had no significant correlations with any of the exercise-induced changes in lung function. Conclusion:? The results showed that in atopic children and adolescents, increased bronchial NO output as well as J’aw(NO) (TMAD) were associated with EIB, while alveolar NO concentration (but not CA(NO) [TMAD]) correlated with the degree of obstruction in smaller airways induced by exercise challenge.

PMID: 22145648 [PubMed – as supplied by publisher]

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Alveolar macrophages modulate allergic inflammation in a murine model of asthma.

Alveolar macrophages modulate allergic inflammation in a murine model of asthma.

Exp Mol Med. 2011 Mar 18;

Authors: Bang BR, Chun E, Shim EJ, Lee HS, Lee SY, Cho SH, Min KU, Kim YY, Park HW

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1b, IL-6 and TNF-?, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.

PMID: 21415590 [PubMed – as supplied by publisher]

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