Eosinophil Major Basic Protein-1 Does Not Contribute to Allergen-Induced Airway Pathologies in Mouse Models of Asthma

Denzler, Karen L.; Farmer, Steven C.; Crosby, Jeff; Borchers, Michael T.; Cieslewicz, Grzegorz; Larson, Kirsten A.; Cormier, Stephania A.; Lee, Nancy A.; Lee, James J.

doi:10.4049/jimmunol.165.10.5509

Cited by 114 publications

(117 citation statements)

References 36 publications

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“…1); this is consistent with similar in vivo models (37,43). An extensive morphological study of eosinophils during allergic inflammation in mice did not show any signs of eosinophil degranulation (44).…”

Section: Discussionsupporting

confidence: 88%

“…These studies include the following: 1) airway eosinophilia can occur without AHR (35); and 2) AHR occurs without airway eosinophilia (12,13,36). AHR also occurred during an allergic response in the absence of murine MBP (37). Furthermore, several studies linked T cell mediators, such as IL-13 and IL-11, but not eosinophils, directly to allergen-induced AHR (15,16,38).…”

Section: Discussionmentioning

confidence: 99%

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Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Kobayashi

Izutsu

Kita

2003

The Journal of Immunology

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Tissue eosinophilia probably plays important roles in the pathophysiology of bronchial asthma and allergic disorders; however, this concept was challenged recently by controversial results in mouse models of bronchial asthma treated with anti-IL-5 Ab and the failure of anti-IL-5 therapy in humans. We have now used a unique model, IL-5 transgenic (TG) mice, to address a fundamental question: is airway eosinophilia beneficial or detrimental in the allergic response? After sensitization and challenge with OVA, IL-5 TG mice showed a marked airway eosinophilia. Surprisingly, these IL-5 TG mice showed lower airway reactivity to methacholine. Immunohistochemical analysis of the lungs revealed a marked peribronchial infiltration of eosinophils, but no eosinophil degranulation. In vitro, mouse eosinophils from peritoneal lavage fluids did not produce superoxide anion, but did produce an anti-inflammatory and fibrotic cytokine, TGF-β1. Indeed, the TGF-β1 levels in bronchoalveolar lavage fluid specimens from IL-5 TG mice directly correlated with airway eosinophilia (r = 0.755). Furthermore, anti-IL-5 treatment of IL-5 TG mice decreased both airway eosinophilia and TGF-β1 levels in bronchoalveolar lavage fluids and increased airway reactivity. Thus, in mice, marked eosinophilia prevents the development of airway hyper-reactivity during an allergic response. Overall, the roles of eosinophils in asthma and in animal models need to be addressed carefully for their potentially detrimental and beneficial effects.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Kobayashi

Izutsu

Kita

2003

The Journal of Immunology

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“…Methylcholine was aerosolized using an ultrasonic nebulizer, and the aerosol was drawn through the chamber at a constant rate for 2 min, after which Penh values were taken for 3 min and averaged. Methylcholine response curves for control animals were consistent with those shown previously for naive 129 mice (24).…”

Section: Airway Physiologysupporting

confidence: 87%

Adenosine-Dependent Airway Inflammation and Hyperresponsiveness in Partially Adenosine Deaminase-Deficient Mice

Chunn¹,

Young²,

Banerjee³

et al. 2001

The Journal of Immunology

136

120

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Adenosine is a signaling nucleoside that is elevated in the lungs of asthmatics. We have engineered a mouse model that has elevated levels of adenosine as a result of the partial expression of the enzyme that metabolizes adenosine, adenosine deaminase (ADA). Mice with lowered levels of ADA enzymatic activity were generated by the ectopic expression of an ADA minigene in the gastrointestinal tract of otherwise ADA-deficient mice. These mice developed progressive lung inflammation and damage and died at 4–5 mo of age from respiratory distress. Associated with this phenotype was a progressive increase in lung adenosine levels. Examination of airway physiology at 6 wk of age revealed alterations in airway hyperresponsiveness. This was reversed following the lowering of adenosine levels using ADA enzyme therapy and also through the use of the adenosine receptor antagonist theophylline, implicating both the nucleoside and its receptors in airway physiological alterations. All four adenosine receptors were expressed in the lungs of both control and partially ADA-deficient mice. However, transcript levels for the A1, A2B, and A3 adenosine receptors were significantly elevated in partially ADA-deficient lungs. There was a significant increase in alveolar macrophages, and monocyte chemoattractant protein-3 was found to be elevated in the bronchial epithelium of these mice, which may have important implications in the regulation of pulmonary inflammation and airway hyperresponsiveness. Collectively, these findings suggest that elevations in adenosine can directly impact lung inflammation and physiology.

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“…Parasagittal sections (4 m) were obtained from paraffin-embedded tissue, stained with hematoxylin and eosin, and analyzed by bright field microscopy. Eosinophil recruitment to lung tissue compartments was determined by immunohistochemistry using a rabbit polyclonal antimouse major basic protein (MBP) antisera (28). Eosinophils surrounding the airways were quantified by counting the number of MBP-positive cells per square millimeter of submucosal tissue surrounding the bronchioles.…”

Section: Methodsmentioning

confidence: 99%

Gα_i2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation

Pero¹,

Borchers

Spicher

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The trafficking of leukocytes from the blood to sites of inflammation is the cumulative result of receptor-ligand-mediated signaling events associated with the leukocytes themselves as well as with the underlying vascular endothelium. Our data show that G␣i signaling pathways in the vascular endothelium regulate a critical step required for leukocyte diapedesis. In vivo studies using knockout mice demonstrated that a signaling event in a non-lymphohematopoietic compartment of the lung prevented the recruitment of proinflammatory leukocytes. Intravital microscopy showed that blockade was at the capillary endothelial surface and ex vivo studies of leukocyte trafficking demonstrated that a G␣i-signaling event in endothelial cells was required for transmigration. Collectively, these data suggest that specific G␣i2-mediated signaling between endothelial cells and leukocytes is required for the extravasation of leukocytes and for tissue-specific accumulation.G proteins ͉ inflammation ͉ knockout mice ͉ leukocyte trafficking ͉ pulmonary models

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Eosinophil Major Basic Protein-1 Does Not Contribute to Allergen-Induced Airway Pathologies in Mouse Models of Asthma

Cited by 114 publications

References 36 publications

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Adenosine-Dependent Airway Inflammation and Hyperresponsiveness in Partially Adenosine Deaminase-Deficient Mice

Gα_i2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation

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Eosinophil Major Basic Protein-1 Does Not Contribute to Allergen-Induced Airway Pathologies in Mouse Models of Asthma

Cited by 114 publications

References 36 publications

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Marked Airway Eosinophilia Prevents Development of Airway Hyper-responsiveness During an Allergic Response in IL-5 Transgenic Mice

Adenosine-Dependent Airway Inflammation and Hyperresponsiveness in Partially Adenosine Deaminase-Deficient Mice

Gαi2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation

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Product

Resources

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Gα_i2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation