Allergen challenge causes inflammation but not goblet cell degranulation in asthmatic subjects

Hays, Steven R.; Woodruff, Prescott G.; Khashayar, Ramin; Ferrando, Ronald E.; Liu, Jane; Fung, Pat; Zhao, Chang Qing; Wong, Hofer; Fahy, John V.

doi:10.1067/mai.2001.119162

Cited by 21 publications

(15 citation statements)

References 31 publications

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“…1) and an increase in the size of submucosal glands [18] in asthmatic airways, resulting in an excessive release of mucus. The increased production of mucus can lead to the formation of plugs that can extend to the membranous bronchioles and contribute to airway obstruction, although, interestingly, mucus release into the BAL fluid was not found to be affected either 1 or 24 h after allergen challenge [19]. Mucin glycoproteins (MUC) are the major macromolecular component of mucus and are expressed as two major forms: membranetethered mucins and secreted mucins.…”

Section: Airway Remodelling In Asthma Epithelial Changesmentioning

confidence: 99%

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Boxall

Holgate²,

Davies³

2006

Eur Respir J

226

187

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Asthma is increasing in prevalence in the developing world, affecting ,10% of the world's population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time.Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-b is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma.This review highlights the role of transforming growth factor-b in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo, however, it is the balance between transforming growth factor-b and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways.A fuller comprehension of the actions of transforming growth factor-b, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.

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Section: Airway Remodelling In Asthma Epithelial Changesmentioning

confidence: 99%

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Boxall

Holgate²,

Davies³

2006

Eur Respir J

226

187

View full text Add to dashboard Cite

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“…The genetic predisposition to develop asthma is now well recognized (20). Numerous studies have also shown the importance of inflammatory cells, such as mast cells, lymphocytes, eosinophils, and neutrophils, as well as Th2 type cytokines in asthma (6,19,32). Interleukin (IL)-4 and IL-13, two Th2 cytokines, are important in immunoglobulin (Ig) class switching to IgE, whereas IL-4 and IL-10 play a crucial role in Th2 cell commitment (9,16,50).…”

mentioning

confidence: 99%

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Careau¹,

Proulx²,

Pouliot³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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-We have previously demonstrated that adoptive transfer of alveolar macrophages from allergy-resistant rats to alveolar macrophage-depleted allergic rats prevents airway hyperresponsiveness development, suggesting an important role for alveolar macrophages in asthma pathogenesis. Given that ovalbumin sensitization can modulate alveolar macrophage cytokine production, we investigated the role of sensitized and unsensitized alveolar macrophages in an asthma model. Alveolar macrophages from unsensitized or sensitized Brown Norway rats were transferred to alveolar macrophage-depleted sensitized rats 24 h before allergen challenge. Airway responsiveness to methacholine and airway inflammation were measured the following day. Methacholine concentration needed to increase lung resistance by 200% was significantly higher in alveolar macrophage-depleted sensitized rats that received unsensitized alveolar macrophages compared with alveolar macrophage-depleted sensitized rats that received sensitized alveolar macrophages. Tumor necrosis factor levels in bronchoalveolar lavage fluid of sensitized rats that received unsensitized alveolar macrophages were significantly lower compared with rats that received sensitized alveolar macrophages. Interestingly, alveolar macrophages of unsensitized animals showed higher phagocytosis activity compared with alveolar macrophages of sensitized rats, suggesting that sensitization modulates alveolar macrophage phagocytosis function. Our data suggest an important role of allergen sensitization on alveolar macrophage function in asthma pathogenesis. airway hyperresponsiveness; cytokine; phagocytosis THE INCIDENCE OF allergic respiratory diseases increased dramatically over the last two decades. The genetic predisposition to develop asthma is now well recognized (20). Numerous studies have also shown the importance of inflammatory cells, such as mast cells, lymphocytes, eosinophils, and neutrophils, as well as Th2 type cytokines in asthma (6,19,32). Interleukin (IL)-4 and IL-13, two Th2 cytokines, are important in immunoglobulin (Ig) class switching to IgE, whereas IL-4 and IL-10 play a crucial role in Th2 cell commitment (9,16,50). In contrast, Th1 cytokines (interferon-␥ and IL-12) protect against asthma development in children (48). Other cytokines, such as tumor necrosis factor (TNF), have been demonstrated to amplify the effect of asthmatic inflammation (29,42). Recently, a role of regulatory T cells (Th3 cells, T R cells, CD4 ϩ CD25 ϩ cells, and natural killer T cells) has been suggested in the control of asthma and allergy, but the specific mechanisms are still unknown (2).Alveolar macrophages (AM) are predominant immune effector cells in the alveolar spaces and conducting airways and play a key role in the immunological homeostasis of the lung (8, 30, 43). Although they are well known to suppress T cell activation and antigen presentation activities of dendritic cells (22,41), their role in asthma is still debated. Using the liposome-mediated macrophage suicide technique (47), we have...

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“…In practical terms, this relies on application of the disector principle [27]. Very few studies of airway inflammation in asthma have adopted stereological approaches [26,[28][29][30] and of these only three have used a disector to enumerate cell density. No such studies appear to have used the optical disector [31][32][33] in thick sections to measure the density of inflammatory cells in actual 3D space.…”

mentioning

confidence: 99%

Do bronchial biopsies represent mast cell density in airways? A stereological study

Carroll

Carroll²

2006

Eur Respir J

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Endobronchial biopsy specimens may not adequately represent inflammatory cell counts throughout the airway wall. The present study aimed to compare mast cell density in biopsies and airway sections using both stereological and nonstereological methods.Post mortem biopsies and adjacent transverse sections were obtained from a mean of five proximal airways per case in 10 subjects who had died of nonrespiratory causes. Tryptasepositive mast cells were measured stereologically in 30-mm sections and nonstereologically in 5-mm sections using an optical disector (cells?mm ), respectively. Reference areas included the inner and total airway wall and to 100 mm below the basement membrane.Case means, based on four or more biopsy sites, significantly correlated with those on transverse sections for counts over the inner airway wall only, using both stereological and nonstereological methods. Cells?mm -3 and cells?mm -2 were significantly correlated within all reference areas. When endobronchial biopsies are obtained from at least four proximal airways per case, intersubject comparisons of mean mast cell density in the inner airway wall are as well represented by counts on biopsies as they are on transverse sections. This is the case using either threedimensional, stereological or two-dimensional, nonstereological methods.

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Allergen challenge causes inflammation but not goblet cell degranulation in asthmatic subjects

Cited by 21 publications

References 31 publications

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Antigen sensitization modulates alveolar macrophage functions in an asthma model

Do bronchial biopsies represent mast cell density in airways? A stereological study

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