A Causative Relationship Exists Between Eosinophils and the Development of Allergic Pulmonary Pathologies in the Mouse

Shen, Hua; Ochkur, Sergei I.; McGarry, Michael P.; Crosby, Jeff; Hines, Edie; Borchers, Michael T.; Wang, Huiying; Biechelle, Travis L.; O'Neill, K.R.; Ansay, Tracy; Colbert, Dana; Cormier, Stephania A.; Justice, J. Paul; Lee, Nancy A.; Lee, James J.

doi:10.4049/jimmunol.170.6.3296

Cited by 153 publications

(124 citation statements)

References 46 publications

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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%

“…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. 17 Fas (CD95), the receptor signaling component of apoptosis, is expressed either constitutively or after activation in a variety of immune cells, such as T cells, B cells, monocytes/macrophages, NK cells, neutrophils, and eosinophils.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Eosinophils are involved in the pathology of allergic asthma (62), but in the CNS they are usually not found except after infection with certain parasites (41). The entry of eosinophils into inflamed tissues is dependent on the cytokine-induced expression of adhesion molecules on endothelial cells and on the expression of chemokines such as CCL1 and CCL11 (10,46).…”

Section: Vol 79 2005 Ifn-␥ Mediates Borna Disease Virus Clearance Fmentioning

confidence: 99%

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Hausmann¹,

Pagenstecher

Baur³

et al. 2005

J Virol

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Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2 k -restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-␥) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-␥-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-␥-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-␥-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-␥ plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-␥ may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.

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“…The second potential mechanism is that anti-CD69 mAb decreases the level of the Th2 cytokine, IL-5. IL-5 is thought to be a crucial regulator of eosinophil proliferation in asthma and other allergic disease (Shen et al, 2003). IL-5 has been shown to activate eosinophils to produce more IL-5 (Spencer et al, 2009), thus forming a positive feedback loop to expand the eosinophil reservoir in peripheral blood and bone marrow reacting to the allergen challenge.…”

Section: Fig 6 Effect Of Anti-cd69 Mab On Ova-induced Ahrmentioning

confidence: 99%

Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma

Wang

Dai

Wang

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:Objective: Airway inflammation and airway hyper-responsiveness (AHR) are principle pathological manifestations of asthma. Cluster of differentiation 69 (CD69) is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody (mAb) on the pathophysiology of a mouse model of asthma. Methods: A murine model of ovalbumin (OVA)-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 μg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1% (0.01 g/ml) OVA on Days 24, 25, and 26. Anti-CD69 mAb or isotype IgG was injected intraperitoneally after OVA challenge; dexamethasone (DXM) was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) in bronchoalveolar lavage fluid (BALF) were also assayed as indices of airway inflammation on Day 28 following OVA injection. Results: Pretreatment with DXM together with anti-CD69 mAb treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti-CD69 mAb did not alter the concentration of BALF GM-CSF. Conclusions: Anti-CD69 mAb treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation.

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A Causative Relationship Exists Between Eosinophils and the Development of Allergic Pulmonary Pathologies in the Mouse

Cited by 153 publications

References 46 publications

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

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

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma

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