scholarly journals Airway Epithelium in Atopic and Nonatopic Asthma: Similarities and Differences

ISRN Allergy ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Prathap Pillai ◽  
Chris J. Corrigan ◽  
Sun Ying
Keyword(s):  
Mast Cells ◽  
Airway Inflammation ◽  
Airway Epithelium ◽  
Inflammatory Cells ◽  
Inflammatory Disorder ◽  
Pathogenic Mechanisms ◽  
Similarities And Differences ◽  
Available Information

Asthma is an inflammatory disorder of the airways, and the airway epithelium has the central role in its pathogenesis. In general, the airway inflammation is characterised by the infiltration of the epithelium and submucosa by a range of inflammatory cells driven largely by Th-2 lymphocytes, eosinophils, and mast cells. The pathogenic mechanisms of nonatopic asthma in comparison to its atopic counterpart have always been a subject of debate. Although clinically are two distinct entities, more similarities than differences have been observed between the two in terms of immunopathogenesis, underlying IgE mechanisms, and so on. in a number of previous studies. More information has become available in recent years comparing the ultrastructure of the epithelium in these two types of asthma. A comparison of airway epithelium in atopic and nonatopic asthma is presented here from the available information in the literature. Similarities outnumber the differences, until we unravel the mystery surrounding these two important phenotypes of asthma in more detail.

scholarly journals Airway Inflammation and the Pathogenesis of Asthma

1994 ◽  
Vol 1 (3) ◽  
pp. 189-195 ◽  
Author(s):  
Paul M O'Byrne
Keyword(s):  
Mast Cells ◽  
Airway Inflammation ◽  
Structural Changes ◽  
Treatment Strategies ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Inflammatory Cell Infiltrate ◽  
Cell Hyperplasia ◽  
Characteristic Type ◽  
Macrophage Colony

Airway inflammation has been recognized for more than l00 years to be present in the airways of patients with severe asthma. Much more recently, airway intlammation has been identified to be central to the pathogenesis of all asthma. The inflammation is of a characteristic type, with the presence of activated eosinophils, mast cells and lymphocytes in bronchoalveolar lavage fluid and airway biopsies from patients with even mild asthma. Stimuli that are known to worsen asthma, such as inhaled allergens, also increase the numbers of mast cells and cosinophils in asthmatic airways. In addition, treatment with inhaled corticoteroids - the most effective treatment for asthma - improves symptoms and reduces the numbers of eosinophil s, mast cells and lymphocytes in the airways. The precise functions of the cells in promoting inflammation and causing asthma symptoms has not yet been fully elucidated. However, it is very likely that eicosanoids, such as the cysteinyl leukotrienes, are produced by eosinophils and mast cells and are a major cause of bronchoconstriction in asthma. Also, these inflammatory cells can produce proinflammatory cytokines, such as granulocytc-macrophage colony-stimulating factor. interleukin (IL) 3 and IL-5, which may promote continuing inflammation in the airways. Lastly, the persisting inflammatory cell infiltrate and products re leased from these cells arc very likely the cause or the airway structural changes characteristic of asthma, such as epithelial damage, goblet cell hyperplasia. smooth muscle thickening and deposition of collagen below the basement membrane. These changes have been suggested tn he the cause of airway hyperresponsiveness in asthma. An improved understanding of the precise mechanisms by which airway inflammation is initiated, propagates and causes airway damage will hopefully allow more precise treatment strategies to he developed for asthma than currently exist.

Histamine as a Modulator of Airway Hyperreactivity L'histamine comme médiateur de l'hyperreactivité des voies aériennes

1987 ◽  
Vol 65 (3) ◽  
pp. 434-434
Author(s):  
John F. Burka
Keyword(s):  
Mast Cells ◽  
Airway Inflammation ◽  
Complex Disease ◽  
Muscle Tone ◽  
Platelet Activating Factor ◽  
Inflammatory Cells ◽  
Airway Hyperreactivity ◽  
Systematic Analysis ◽  
Inflammatory Reactions

Histamine has long been known as a bronchoconstrictor agonist, but its role in asthma and airway inflammation is not as clear. Histamine release occurs in response to allergic challenge of mast cells. However, it is now known that mast cells are heterogeneous in responsiveness and sensitivity to antiallergic agents. Other cells, such as alveolar macrophages, neutrophils, eosinophils, and lymphocytes, can also be activated during allergic and inflammatory reactions. Damage to the airway epithelium would reduce the release of an epithelium-derived relaxant factor and thus increase airway smooth muscle tone. Released mediators, including eicosanoids, platelet-activating factor (PAF), complement fragments, and neurotransmitters, also contribute to inflammation in the airways and the interaction of all these mediators complicates the interpretation of the role of individual mediators. Not only can individual mediators affect the biological activity of other mediators, but their synthesis and release can be modulated as well.The present symposium was organized to examine the putative role of histamine in airway hyperreactivity and how it might interact with other mediators. Papers were presented on the role of mast cells and epithelial cells in allergic bronchoconstriction. The interaction of mast cells with other inflammatory cells was also reviewed. Further information was presented on the biological characteristics of epithelium-derived relaxant factor. Other papers reviewed the interaction of mediators on bronchoconstrictor activity and in inflammation-induced changes in microvascular permeability. The speakers emphasized that asthma and other forms of airway inflammation are complex disease entities and that a systematic analysis of interactions between the cells and mediators in the airways is necessary to understand the aetiology of these diseases and to develop improved therapeutic regimens.This symposium was supported by the Pharmacological Society of Canada, the Canadian Histamine Association, the Upjohn Company of Canada, and Merck Frosst Canada Inc.

scholarly journals Effects of Obesity on Airway and Systemic Inflammation in Asthmatic Children

2021 ◽  
pp. 1-11
Author(s):  
Emine Vezir ◽  
Ersoy Civelek ◽  
Emine Dibek Misirlioglu ◽  
Muge Toyran ◽  
Murat Capanoglu ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Systemic Inflammation ◽  
Adiponectin Level ◽  
Inflammatory Cells ◽  
Prick Test ◽  
Asthmatic Children ◽  
Asthmatic Patients ◽  
Reactive Protein ◽  
Type 2 Cytokines ◽  
Asthma In Children

Background: Obese asthma is a complex syndrome with certain phenotypes that differ in children and adults. There is no clear evidence regarding the presence of additive or synergistic pathological interaction between obesity and asthma in children. Objectives: Our aim was to demonstrate the interaction of obesity and asthma in children in terms of airway and systemic inflammation by a controlled observational study. Methods: Four groups were formed: asthma obese (AO), asthma nonobese (ANO), non-AO (NAO), nonasthma nonobese (NANO). Spirometry test, fractional exhaled nitric oxide (FeNO) test, skin prick test, serum inflammatory biomarkers (C-reactive protein, C3, C4, adiponectin, leptin, resistin, periostin, YKL-40, Type 1, and Type 2 cytokines) were conducted and evaluated in all participants. Sputum inflammatory cells (sputum eosinophils and neutrophils) were evaluated in patients who could produce induced sputum and obesity-asthma interactions were determined. Results: A total of 153 participants aged 6–18 years were included in the study, including the AO group (n = 46), the ANO group (n = 45), the NAO group (n = 30), and the NANO group (n = 32). IL-4 (p < 0.001), IL-5 (p < 0.001), IL-13 (p < 0.001), resistin (p < 0.001), and YKL-40 (p < 0.001) levels were higher in patients with asthma independent of obesity. The lowest adiponectin level was found in the AO group and obesity-asthma interaction was detected (p < 0.001). Sputum eosinophilia (p < 0.01), sputum neutrophilia (p < 0.01), and FeNO levels (p = 0.07) were higher in asthmatic patients independent of obesity. In the group with paucigranulocytic inflammation, resistin and YKL-40 levels were significantly lower than in the group without paucigranulocytic inflammation (p < 0.01). Conclusion: No interaction was found between obesity and asthma in terms of airway inflammation. Interaction between obesity and asthma was shown in terms of adiponectin level and resistin/adiponectin and leptin/adiponectin ratios. It was found that serum YKL-40 and resistin levels could be associated with airway inflammation.

Childhood Asthma: Update

1992 ◽  
Vol 13 (11) ◽  
pp. 403-412
Author(s):  
Gail G. Shapiro
Keyword(s):  
Smooth Muscle ◽  
Mast Cells ◽  
Airway Inflammation ◽  
Immunoglobulin E ◽  
Bronchial Hyperresponsiveness ◽  
Basement Membrane Thickening ◽  
Infiltrating Cells ◽  
Lung Biopsies ◽  
Airways Reactivity ◽  
Mast Cell Mediator Release

Definition and Pathophysiology Asthma is a reversible airways disease characterized by both smooth muscle hyperreactivity and airway inflammation. During the 1970s and early 1980s the focus was on smooth muscle constriction, and it was believed that better bronchodilators would greatly diminish our difficulties in controlling this condition. This, unfortunately, was not the case. The emphasis of therapy today has turned to airway inflammation. Lung biopsies from patients who have asthma show destruction of respiratory epithelium, basement membrane thickening, and inflammatory cellular infiltrate. Among the infiltrating cells are eosinophils, macrophages, and neutrophils that are called to the site of inflammation by the chemotactic products released by activated mast cells. Upon their arrival, these cells release their own products of inflammation, which amplify this immunologic response. A variety of neuropeptides also play a role, some serving to stabilize and others to destabilize the airway. One result of this airway inflammation is airways reactivity, also known as bronchial hyperresponsiveness. A common example of this scenario is the child who has allergic asthma and encounters a problematic allergen. This child has immunoglobulin E (IgE) to this allergen bound to mast cells in his or her airway. Upon exposure to the allergen, the binding of IgE and antigen triggers mast cell mediator release within minutes.

scholarly journals Migration of human inflammatory cells into the lung results in the remodeling of arachidonic acid into a triglyceride pool.

1995 ◽  
Vol 182 (5) ◽  
pp. 1181-1190 ◽  
Author(s):  
M Triggiani ◽  
A Oriente ◽  
M C Seeds ◽  
D A Bass ◽  
G Marone ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Mast Cells ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Adult Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Inflammatory Cells ◽  
Lipid Bodies ◽  
Blood Neutrophils ◽  
High Concentrations

Increasing evidence suggests that the metabolism of arachidonic acid (AA) may be different in inflammatory cells isolated from blood or migrating into tissues. To explore the possibility that changes in AA metabolism between blood and tissue inflammatory cells could be due in part to a different content or distribution of AA in glycerolipid classes, we studied these parameters in six human inflammatory cells isolated from blood (eosinophils, monocytes, neutrophils, and platelets) or from the lung tissue (mast cells and macrophages). Lung cells generally had a higher total cellular content of AA than that found in the blood cells. In addition, both mast cells and macrophages had a large endogenous pool of AA associated with triglycerides (TG), containing 45 and 22% of their total cellular AA, respectively. To address the hypothesis that cells migrating into the lung had a higher cellular level of AA and a larger AA pool in TG, we studied neutrophils isolated from the bronchoalveolar lavage (BAL) of patients with adult respiratory distress syndrome. BAL neutrophils had a fourfold increase in cellular AA as compared with blood neutrophils and contained 25% of their AA in TG versus 3% in blood neutrophils. BAL neutrophils also had a higher number of cytoplasmic lipid bodies (8 +/- 3/cell) relative to blood neutrophils (2 +/- 1/cell). High concentrations of free AA were also found in the cell-free BAL fluid of adult respiratory distress syndrome patients. To explore whether changes in BAL neutrophils may be due to the exposure of the cells to high concentrations of exogenous AA found in BAL, we incubated blood neutrophils in culture with AA (10-100 microM) for 24 h. Neutrophils supplemented with AA had a 10-fold increase in the amount of AA associated with TG and a sixfold increase in the number of lipid bodies. In addition, supplementation with AA induced a dose-dependent formation of hypodense cells. Taken together, these data indicate that human inflammatory cells undergo a fundamental and consistent remodeling of AA pools as they mature or enter the lung from the blood. These biochemical and morphological changes can be mimicked in vitro by exposing the cells to high levels of AA. This mechanism may be responsible for the changes in AA mobilization and eicosanoid metabolism observed in tissue inflammatory cells.

Blocking ATP releasing channels prevents high extracellular ATP levels and airway hyperreactivity in an asthmatic mouse model

2021 ◽  
Author(s):  
Llilian Arzola Martínez ◽  
Rebeca Benavente ◽  
Génesis Vega ◽  
Mariana Ríos ◽  
Wendy Fonseca ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Epithelium ◽  
Atp Release ◽  
Specific Inhibitor ◽  
Extracellular Atp ◽  
Airway Hyperreactivity ◽  
Luciferase Assay ◽  
Asthmatic Patients ◽  
Allergic Mouse

Allergic asthma is a chronic airway inflammatory response to different triggers like inhaled allergens. Excessive ATP in fluids from asthmatic patients is considered an inflammatory signal and an important autocrine/paracrine modulator of airway physiology. Here we investigated the deleterious effect of increased extracellular ATP (eATP) concentration on the mucociliary clearance (MCC) effectiveness and determined the role of ATP releasing channels during airway inflammation in an ovalbumin (OVA)-sensitized mouse model. Our allergic mouse model exhibited high levels of eATP measured in the tracheal fluid with a luciferin-luciferase assay and reduced MCC velocity determined by microspheres tracking in the trachea ex vivo. Addition of ATP had a dual effect on MCC, where lower ATP concentration (µM) increased microspheres velocity, while higher concentration (mM) transiently stopped microspheres movement. Also, an augmented ethidium bromide uptake by the allergic tracheal airway epithelium suggests an increase in ATP release channel functionality during inflammatory conditions. The use of carbenoxolone, a non-specific inhibitor of connexin and pannexin1channels reduced the eATP concentration in the allergic mouse tracheal fluid and dye uptake by the airway epithelium, providing evidence that these ATP release channels are facilitating the net flux of ATP to the lumen during airway inflammation. However, only the specific inhibition of pannexin1 with 10Panx peptide significantly reduced eATP in bronchoalveolar lavage and decreased airway hyperresponsiveness in OVA-allergic mouse model. These data provide evidence that blocking eATP may be a pharmacological alternative to be explored in rescue therapy during episodes of airflow restriction in asthmatic patients.

scholarly journals HDAC2 attenuates airway inflammation by suppressing IL-17A production in HDM-challenged mice

2019 ◽  
Vol 316 (1) ◽  
pp. L269-L279 ◽  
Author(s):  
Tianwen Lai ◽  
Mindan Wu ◽  
Chao Zhang ◽  
Luanqing Che ◽  
Feng Xu ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Cytokines ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Protective Role ◽  
In Vivo Models

Histone deacetylase (HDAC)2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly understood. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of house dust mite (HDM)-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL-17A, or both. We observed that HDM-challenged Hdac2+/− mice exhibited substantially enhanced infiltration of inflammatory cells. Higher levels of T helper 2 cytokines and IL-17A expression were found in lung tissues of HDM-challenged Hdac2+/− mice. Interestingly, IL-17A deletion or anti-IL-17A treatment reversed the enhanced airway inflammation induced by HDAC2 impairment. In vitro, HDM and IL-17A synergistically decreased HDAC2 expression in HBE cells. HDAC2 gene silencing further enhanced HDM- and/or IL-17A-induced inflammatory cytokines in HBE cells. HDAC2 overexpresion or blocking IL-17A gene expression restored the enhanced inflammatory cytokines. Collectively, these results support a protective role of HDAC2 in HDM-induced airway inflammation by suppressing IL-17A production and might suggest that activation of HDAC2 and/or inhibition of IL-17A production could prevent the development of allergic airway inflammation.

scholarly journals Antagonistic Peptides That Specifically Bind to the First and Second Extracellular Loops of CCR5 and Anti-IL-23p19 Antibody Reduce Airway Inflammation by Suppressing the IL-23/Th17 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yingli Zhang ◽  
Rongrong Liang ◽  
Aicen Xie ◽  
Wenqian Shi ◽  
Huarong Huang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Inflammatory Disorder ◽  
Mrna Levels ◽  
T Helper 17 ◽  
Mucus Production ◽  
Chronic Inflammatory Disorder ◽  
Extracellular Loops

Asthma is a heterogeneous chronic inflammatory disorder of the airways with a complex etiology, which involves a variety of cells and cellular components. Therefore, the aim of the study was to investigate the effects and mechanisms of antagonistic peptides that specifically bind to the first and second extracellular loops of CCR5 (GH and HY peptides, respectively) and anti-interleukin-23 subunit p19 (anti-IL-23p19) in the airway and thereby mediate inflammation and the IL-23/T helper 17 (Th17) cell pathway in asthmatic mice. An experimental asthma model using BALB/c mice was induced by ovalbumin (OVA) and treated with peptides that are antagonistic to CCR5 or with anti-IL-23p19. The extents of the asthmatic inflammation and mucus production were assessed. In addition, bronchoalveolar lavage fluid (BALF) was collected, the cells were counted, and the IL-4 level was detected by ELISA. The IL-23/Th17 pathway-related protein and mRNA levels in the lung tissues were measured, and the positive production rates of Th17 cells in the thymus, spleen, and peripheral blood were detected. The groups treated with one of the two peptides and/or anti-IL-23p19 showed significant reductions in allergic inflammation and mucus secretion; decreased expression levels of IL-23p19, IL-23R, IL-17A and lactoferrin (LTF); and reduced proportions of Th17 cells in the thymus, spleen, and peripheral blood. Specifically, among the four treatment groups, the anti-IL-23p19 with HY peptide group exhibited the lowest positive production rate of Th17 cells. Our data also showed a significant and positive correlation between CCR5 and IL-23p19 protein expression. These findings suggest that the administration of peptides antagonistic to CCR5 and/or anti-IL-23p19 can reduce airway inflammation in asthmatic mice, most likely through inhibition of the IL-23/Th17 signaling pathway, and the HY peptide can alleviate inflammation not only through the IL-23/Th17 pathway but also through other mechanisms that result in the regulation of inflammation.

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