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.

scholarly journals Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Lixia Wang ◽  
Binshan Zha ◽  
Qiying Shen ◽  
Hongyun Zou ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Cell ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Th2 Response ◽  
Cell Hyperplasia ◽  
Mucus Production ◽  
Caspase 1 ◽  
Nlrp3 Expression

Background. Our colleagues have demonstrated an impressive therapeutic role of sevoflurane in a murine allergic airway inflammation model, but the mechanisms underlying this effect remain undefined. In this study, we tried to investigate the effect of sevoflurane on the resolution of allergic airway inflammation and to assess whether NLRP3 or the NLRP3 inflammasome is involved in this process. Methods. Female (C57BL/6) mice were sensitized and challenged with ovalbumin (OVA). Then, some of the mice received MCC950 (10 mg/kg; i.p.) or 3% sevoflurane. Total and differential inflammatory cell numbers, proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), the peribronchial inflammation density, and mucus production were evaluated. In addition, we analysed the protein levels of NLRP3, the apoptosis-associated speck-like protein containing the caspase activation and recruitment domain (ASC), pro-caspase-1, and caspase-1 in the lung tissue. Results. We found that OVA-induced inflammatory cell recruitment to peribronchial regions, goblet cell hyperplasia, the serum levels of IgE, inflammatory cells, and the Th2 cytokine secretion in BALF was potently suppressed by sevoflurane with an efficacy comparable with that suppressed by MCC950 treatment. Furthermore, sevoflurane, similar to MCC950, clearly inhibited the OVA-induced activity of NLRP3 in the lungs. In addition, we found that OVA challenge failed to increase the expression of ASC, pro-caspase-1, and caspase-1 in the lungs and the levels of IL-18 and IL-1β in BALF. Conclusion. Taken together, our data showed that sevoflurane ameliorated allergic airway inflammation by inhibiting Th2 responses and NLRP3 expression. The NLRP3 independent of inflammasomes participated in the pathogenesis of allergic asthma in this model.

Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation

2009 ◽  
Vol 296 (1) ◽  
pp. L30-L36 ◽  
Author(s):  
Masakata Yoshioka ◽  
Hironori Sagara ◽  
Fumiyuki Takahashi ◽  
Norihiro Harada ◽  
Kazuto Nishio ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Mast Cells ◽  
Airway Inflammation ◽  
Biological Significance ◽  
Allergic Airway Inflammation ◽  
Lavage Fluid ◽  
Allergic Airway Disease ◽  
Cell Hyperplasia ◽  
Murine Bone Marrow ◽  
Ige Mediated

Multidrug resistance-associated protein 1 (MRP1) is a cysteinyl leukotriene (CysLT) export pump expressed on mast cells. CysLTs are crucial mediators in allergic airway disease. However, biological significance of MRP1 in allergic airway inflammation has not yet been elucidated. In this study, we sensitized wild-type control mice ( mrp1+/+) and MRP1-deficient mice ( mrp1−/−) to ovalbumin (OVA) and challenged them with OVA by aerosol. Airway inflammation and goblet cell hyperplasia after OVA exposure were reduced in mrp1−/− mice compared with mrp1+/+ mice. Furthermore, CysLT levels in bronchoalveolar lavage fluid (BALF) from OVA-exposed mrp1−/− mice were significantly lower than those from OVA-exposed mrp1+/+ mice. Levels of OVA-specific IgE, IL-4, and IL-13 in BALF were also decreased in OVA-exposed mrp1−/− mice. IgE-mediated release of CysLTs from murine bone marrow-derived mast cells was markedly impaired by MRP1 deficiency. Our results indicate that MRP1 plays an important role in the development of allergic airway inflammation through regulation of IgE-mediated CysLT export from mast cells.

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.

Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma

2016 ◽  
Vol 44 (01) ◽  
pp. 133-147 ◽  
Author(s):  
Chen-Chen Lee ◽  
Yueh-Lun Lee ◽  
Chien-N Wang ◽  
Hsing-Chuan Tsai ◽  
Chun-Lung Chiu ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Oral Feeding ◽  
Inflammatory Cell Infiltrate ◽  
Dependent Manner ◽  
Polygonum Multiflorum ◽  
Mucus Production

The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME’s mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation.

Early pulmonary response in rats infected with Trichinella spiralis

Parasitology ◽  
2006 ◽  
Vol 134 (2) ◽  
pp. 281-288 ◽  
Author(s):  
S. M. VENTURIELLO ◽  
M. L. VERZOLETTI ◽  
S. N. COSTANTINO ◽  
M. A. FORASTIERO ◽  
M. E. ROUX
Keyword(s):  
Bronchoalveolar Lavage ◽  
Lymphoid Tissue ◽  
Striated Muscle ◽  
Trichinella Spiralis ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Cell Phenotype ◽  
Cell Hyperplasia ◽  
Pulmonary Response ◽  
Pulmonary Parenchyma

The migratory stage of Trichinella spiralis, the newborn larva, travels along the pulmonary microvascular system on its way to the striated muscle cells. In the present study, an important inflammatory reaction was observed on days 5 and 14 post-infection (p.i.) in the lungs of infected rats. This inflammation was characterized by a Th2 cell phenotype of hyperplastic bronchus-associated lymphoid tissue and by goblet cell hyperplasia. Among the inflammatory cells were eosinophils and mast cells scattered over the pulmonary parenchyma. On day 5 p.i. the number of IgE+, CD4+ and CD5+ cells in the bronchus-associated lymphoid tissue were increased and IgE-secreting lung cells were also detected. At the end of the migratory phase of the infection (day 14 p.i.), only IgE+ cells were detected in high numbers and in the bronchoalveolar lavage fluid, an increment in the total IgE levels as well as the presence of IgE and IgA anti-larvae surface were also detected. In cytotoxicity assays, cells from the bronchoalveolar lavage had considerable biological activity since they were able to kill the larvae even in the absence of specific antibodies. These results show that the lung is an organ involved in the immune response developed early during a T. spiralis infection and suggest its importance in the protection of the host.

scholarly journals Effects of Laminaria japonica polysaccharides on airway inflammation of lungs in an asthma mouse model

2015 ◽  
Vol 10 ◽  
Author(s):  
Rongjun Lin ◽  
Xiaomei Liu ◽  
Yan Meng ◽  
Mei Xu ◽  
Jianping Guo
Keyword(s):  
Airway Inflammation ◽  
Laminaria Japonica ◽  
Inflammatory Cells ◽  
Serum Levels ◽  
Lavage Fluid ◽  
Chronic Inflammatory Disease ◽  
Serum Ige ◽  
Asthma Model ◽  
Group A ◽  
Tgf Β1

Background: Asthma is a serious chronic inflammatory disease affecting 300 million people worldwide. This aim of this study to investigate the anti-inflammatory and anti-asthmatic effects of Laminaria japonica extract in the ovalbumin (OVA)-induced mouse asthma model. Methods: A mouse asthma model was established in SPF Kunming mice by OVA-sensitization followed by inhalation of aerosol allergen for two weeks. Laminaria japonica polysaccharides (LJPS) were given by gavage feeding at 50 mg/kg/day during OVA inhalation challenge period, and their effect on asthma was compared with the standard treatment of Budesonide inhalation. The total inflammatory cells and eosinophils in bronchoalveolar lavage fluid (BALF) were determined. Histopathological changes in lung tissue were studied and scored to determine the degree of inflammation. Levels of IL-12, IL-13, and TGF-β1 in BALF as well as serum levels of IgE were measured. Expressions of IL-12, IL-13, and TGF-β1 in lung tissues were assessed. Results: Highly inflammatory lungs infiltrated with significant increased eosinophils were observed in OVAinduced asthmatic mice. The OVA treated mice presented with a lower level of IL-12 and higher levels of IL-13 and TGF-β1 in BALF and lung tissues, as well as an increased level of the serum IgE. Treatment with LJPS (Group B) significantly decreased the numbers of eosinophils in the BALF (P<0.05) and alleviated lung inflammation compared to the untreated asthma mice (Group A). It also reduced the serum IgE levels, increased expression of IL-12, and decreased the expression of IL-13 and TGF-β1 in BALF and lung (Both P < 0.05) compared with the group A. Conclusions: LJPS can significantly inhibit airway inflammation of asthmatic mice, adjust the balance of cytokines, and improve the pulmonary histopathological condition. Our data suggested that LJPS might be a potential therapeutic reagent for allergic asthma.

scholarly journals Effects of caffeoylxanthiazonoside on airway inflammation in an allergic asthma mice model

2021 ◽  
Vol 18 (4) ◽  
pp. 761-766
Author(s):  
Qian Wu ◽  
Hui Wang ◽  
Xiaowen Che ◽  
Wei Wang
Keyword(s):  
Protein Expression ◽  
Western Blot ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
The Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Ifn Γ

Purpose: To investigate the inhibitory effects of caffeoylxanthiazonoside (CYT) on airway inflammation in mice and its mechanism of action. Methods: An allergic asthma mice model was established by intraperitoneal injection and aerosol nebulization with ovalbumin (OVA). After treatment with CYT, the blood and bronchoalveolar lavage fluid (BALF) were collected from the mice. The leukocytes were classified and counted with Giemsa solution. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of IgE, and IL-4, IL-5, IL-13 and IFN-γ in the BALF of mice. Lung tissues were obtained from the mice and MUC5AC protein expression was measured by western blot. Results: CYT significantly decreased the serum level of IgE in asthmatic mice. Inflammatory cells in BALF of mice were markedly reduced (p < 0.05) by CYT treatment at varying doses (10, 20, and 40 mg/kg). Treatment with CYT also significantly suppressed the cytokines of IL-4, IL-5 and IL-13 and increased the IFN-γ in the BLAF of OVA-induced allergic asthma mice (p < 0.05). Western blot results indicate that CYT treatment significantly decreased the expression of MUC5AC protein in the lung tissues of asthmatic mice. In addition, no significant effects on the body weight of the mice were found after CYT treatment. Conclusion: Caffeoylxanthiazonoside inhibits airway inflammation in allergic asthma mice by altering Th1/Th2 via re-balancing of related cytokines and downregulation of lung MUC5AC protein expression. Therefore, this compound can potentially be developed for the therapeutic management of inflammation in allergic asthma.

scholarly journals Reduction of Airway Hyperresponsiveness by KWLL inDermatophagoides-pteronyssinus-Challenged Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-9
Author(s):  
Chih-Che Lin ◽  
Shulhn-Der Wang ◽  
Li-Jen Lin ◽  
Hong-Jye Hong ◽  
Chin-Jen Wu ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Bronchoalveolar Lavage Fluid ◽  
Expression Profiles ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Eosinophil Infiltration ◽  
Cell Hyperplasia ◽  
Ancient Civilizations ◽  
Airway Hypersensitivity

Urine therapy has been commonly practiced in ancient civilizations including those of India, China, and Greece. The traditional Chinese medicine KWLL, the precipitation of human urine, has been used in China to alleviate the symptoms of asthma for thousands of years. However, the mechanism of action by which KWLL exerts its immunotherapy is unclear. This study attempted to elucidate the pharmacology of KWLL in mice that had been challenged recurrently byDermatophagoides pteronyssinus(Der p). BALB/c mice were orally administered KWLL (1 g/kg) before an intratracheal (i.t.) challenge of Der p. Allergic airway inflammation and remodeling were provoked by repetitive Der p (50 μg/mice) challenges six times at 1 wk intervals. Airway hypersensitivity, histological lung characteristics, and the expression profiles of cytokines and various genes were assessed. KWLL reduced Der p-induced airway hyperresponsiveness and inhibited eosinophil infiltration by downregulating the protein expression of IL-5 in bronchoalveolar lavage fluid (BALF). It also inhibited neutrophil recruitment by downregulating IL-17A in BALF. KWLL effectively diminished inflammatory cells, goblet cell hyperplasia, and mRNA expression of IL-6 and IL-17A in the lung. The reduction by KWLL of airway inflammatory and hyperresponsiveness in allergic asthmatic mice was mediated via immunomodulation of IL-5, IL-6, and IL-17A.

scholarly journals Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice

2005 ◽  
Vol 202 (1) ◽  
pp. 47-59 ◽  
Author(s):  
Tirumalai Rangasamy ◽  
Jia Guo ◽  
Wayne A. Mitzner ◽  
Jessica Roman ◽  
Anju Singh ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Leucine Zipper ◽  
Allergen Challenge ◽  
Lavage Fluid ◽  
Related Factor ◽  
Cell Hyperplasia ◽  
Basic Leucine Zipper ◽  
Mucus Cell ◽  
Antioxidant Genes ◽  
Asthmatic Response

Oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect in antioxidant responses has been speculated to exacerbate asthma severity, this has been difficult to demonstrate with certainty. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive basic leucine zipper transcription factor that is involved in the transcriptional regulation of many antioxidant genes. We show that disruption of the Nrf2 gene leads to severe allergen-driven airway inflammation and hyperresponsiveness in mice. Enhanced asthmatic response as a result of ovalbumin sensitization and challenge in Nrf2-disrupted mice was associated with more pronounced mucus cell hyperplasia and infiltration of eosinophils into the lungs than seen in wild-type littermates. Nrf2 disruption resulted in an increased expression of the T helper type 2 cytokines interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid and in splenocytes after allergen challenge. The enhanced severity of the asthmatic response from disruption of the Nrf2 pathway was a result of a lowered antioxidant status of the lungs caused by lower basal expression, as well as marked attenuation, of the transcriptional induction of multiple antioxidant genes. Our studies suggest that the responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma.

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