Anti-interleukin 5 But Not Anti-IgE Prevents Airway  Inflammation and Airway Hyperresponsiveness

Hamelmann, Eckard; Cieslewicz, G.; Schwarze, Jürgen; Ishizuka, Tamotsu; Joetham, Anthony; Heusser, C H; Gelfand, Erwin W.

doi:10.1164/ajrccm.160.3.9806029

Cited by 140 publications

(101 citation statements)

References 30 publications

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“…Peribronchial lymph node (PBLN) cells were purified, as previously described (26). Cells were plated at 4 ϫ 10 5 /ml in 96-well round-bottom tissue culture plates in triplicate and incubated with medium alone or OVA (100 g/ml) for 48 h in a humidified atmosphere of 5% CO 2 at 37°C.…”

Section: In Vitro Cytokine Production Assaysmentioning

confidence: 99%

Effect of Microbial Heat Shock Proteins on Airway Inflammation and Hyperresponsiveness

Rha

Taube

Haczku

et al. 2002

The Journal of Immunology

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Microbial heat shock proteins (hsp) have been associated with the generation and induction of Th1-type immune responses. We tested the effects of treatment with five different microbial hsp (Mycobacterium leprae, Streptococcus pneumoniae, Helicobacter pylori, bacillus Calmette-Guérin, and Mycobacterium tuberculosis) in a murine model of allergic airway inflammation and airway hyperresponsiveness (AHR). Mice were sensitized to OVA by i.p. injection and then challenged by OVA inhalation. Hsp were administered to each group by i.p. injection before sensitization and challenge. Sensitized and challenged mice developed increased serum levels of OVA-specific IgE with significant airway eosinophilia and heightened responsiveness to methacholine when compared with nonsensitized animals. Administration of M. leprae hsp prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia in a dose-dependent manner. Treatment with M. leprae hsp also resulted in suppression of IL-4 and IL-5 production in bronchoalveolar lavage fluid, while IL-10 and IFN-γ production were increased. Furthermore, M. leprae hsp treatment significantly suppressed OVA-specific IgE production and goblet cell hyperplasia/mucin hyperproduction. In contrast, treatment with the other hsp failed to prevent changes in airway responsiveness, lung eosinophilia, or cytokine production. Depletion of γ/δ T lymphocytes before sensitization and challenge abolished the effect of M. leprae hsp treatment on AHR. These results indicate selective and distinctive properties among the hsp, and that M. leprae hsp may have a potential therapeutic role in the treatment of allergic airway inflammation and altered airway function.

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Section: In Vitro Cytokine Production Assaysmentioning

confidence: 99%

Effect of Microbial Heat Shock Proteins on Airway Inflammation and Hyperresponsiveness

Rha

Taube

Haczku

et al. 2002

The Journal of Immunology

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“…5 The eosinophil is thought to be a major effector cell in the pathogenesis of allergen-mediated AHR. [6][7][8][9] In particular, the release of cytotoxic granule proteins, such as major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO), which can damage the airway epithelium, contribute to this phenomenon. 2 IL-13 is thought to induce AHR in the allergic lung by directly affecting epithelial cells 10 or by recruiting eosinophil via an IL-5-and eotaxin-dependent mechanism.…”

Section: Introductionmentioning

confidence: 99%

“…11,12 However, the transfer of eosinophils to IL-5 À/À mice overcomes the intrinsic defect in T cell IL-13 production 13 and induces the development of AHR. 8 Thus, although the role of IL-5 in AHR is controversial, [6][7][8][9][14][15][16] the relationship between eosinophils and AHR is still correlative. 8,[11][12][13] Apoptosis is an important mechanism for the maintenance of homoeostasis in the immune system.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Chuang¹,

Cl²,

et al. 2004

Gene Ther

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Allergic asthma is characterized by airway hyper-responsiveness (AHR) and cellular infiltration of the airway with predominantly eosinophils and Th2 cells. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligandmediated apoptosis. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. To examine the effect of the FasL gene on airway inflammation and immune effector cells in allergic asthma, recombinant adenovirus expressing murine FasL (Ad-FasL) was delivered intratracheally into ovalbumin (OVA)-immunized mice. We found that a single administration of Ad-FasL in OVA-immunized mice significantly alleviated AHR and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-a production also decreased in AdFasL-treated OVA-immunized mice. These findings indicated that the administration of Ad-FasL to OVA-sensitized mice significantly suppressed pulmonary allergic responses. Although more studies are needed, these results suggested that Ad-FasL might be applied as an alternative therapy for allergic asthma.

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“…These cell surface-bound IgE molecules can subsequently become cross-linked upon binding to the Ag, resulting in mast cell activation and the release of a plethora of pro-inflammatory molecules. However, allergic airway inflammation and AHR can be elicited in mice in the absence of IgE (22,23) or all classes of Abs (24). The existing literature suggests that a role for IgE or other classes of Abs in murine models of asthma is dependent on experimental variables.…”

mentioning

confidence: 99%

IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models

Mayr

Zuberi

Zhang

et al. 2002

The Journal of Immunology

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We have studied murine models of asthma using FcεRIα-chain-deficient (FcεRIα−/−) mice to investigate the role of IgE-dependent mast cell activation in these models. When mice were either 1) immunized once with OVA in alum i.p. and then challenged with OVA intranasally, or 2) repeatedly immunized with OVA in the absence of adjuvant and subsequently challenged with nebulized OVA, FcεRα−/− mice had significantly fewer eosinophils and lower IL-4 levels in their bronchoalveolar lavage fluid compared with wild-type mice. When mice were given anti-IL-5 antibody before OVA challenge in protocol 1, eosinophilic infiltration into the airways was significantly suppressed in both genotypes, but only FcεRIα−/− mice showed significantly reduced airway hyperresponsiveness (AHR). In addition, when mice immunized and challenged with OVA also received a late OVA provocation at a higher concentration and were then exposed to methacholine, only wild-type mice developed a substantial increase in AHR. Since FcεRI is expressed mainly on mast cells in mouse airways, we conclude that IgE-dependent activation of this cell type plays an important role in the development of allergic airway inflammation and AHR in mice. The models used may be of value for testing inhibitors of IgE or mast cells for development of therapeutic agents for human asthma.

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Anti-interleukin 5 But Not Anti-IgE Prevents Airway Inflammation and Airway Hyperresponsiveness

Cited by 140 publications

References 30 publications

Effect of Microbial Heat Shock Proteins on Airway Inflammation and Hyperresponsiveness

Effect of Microbial Heat Shock Proteins on Airway Inflammation and Hyperresponsiveness

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models

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