Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.
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TLDR
Results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.Abstract:
Airways inflammation is thought to play a central role in the pathogenesis of asthma. However, the precise role that individual inflammatory cells and mediators play in the development of airways hyperreactivity and the morphological changes of the lung during allergic pulmonary inflammation is unknown. In this investigation we have used a mouse model of allergic pulmonary inflammation and interleukin (IL) 5-deficient mice to establish the essential role of this cytokine and eosinophils in the initiation of aeroallergen-induced lung damage and the development of airways hyperreactivity. Sensitization and aerosol challenge of mice with ovalbumin results in airways eosinophilia and extensive lung damage analogous to that seen in asthma. Aeroallergen-challenged mice also display airways hyperreactivity to beta-methacholine. In IL-5-deficient mice, the eosinophilia, lung damage, and airways hyperreactivity normally resulting from aeroallergen challenge were abolished. Reconstitution of IL-5 production with recombinant vaccinia viruses engineered to express this factor completely restored aeroallergen-induced eosinophilia and airways dysfunction. These results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.read more
Citations
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Eosinophil degranulation in the allergic lung of mice primarily occurs in the airway lumen.
Kristopher Clark,Ljubov Simson,Nicole Newcombe,Aulikki Koskinen,Joerg Mattes,Nancy A. Lee,James J. Lee,Lindsay A. Dent,Klaus I. Matthaei,Paul S. Foster,Paul S. Foster +10 more
TL;DR: Estimation of the degree of eosinophil activation in the bone marrow, blood, lung tissue, and airways lumen of ovalbumin‐sensitized and aero‐challenged wild‐type and interleukin‐5 transgenic mice found that it was most prominent in and primarily compartmentalized to the airway lumen.
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CD23 and Allergic Pulmonary Inflammation: Potential Role as an Inhibitor
Manuela Cernadas,George T. De Sanctis,S J Krinzman,David A. Mark,Carolyn E. Donovan,James A. Listman,Lester Kobzik,Hitoshi Kikutani,David C. Christiani,David L. Perkins,Patricia W. Finn +10 more
TL;DR: It is suggested that CD23 negatively regulates pulmonary inflammation and airway hyperreactivity on the basis of a model that the anti-CD23 mAb transduces, whereas the Fab fragment inhibits, CD23 signaling.
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Targeting eosinophil biology in asthma therapy.
TL;DR: A critical overview about further candidate molecules involved in the regulation of eosinophil recruitment, chemotaxis, activation, survival, and apoptosis that have been recently discussed as targets for an eosInophil-specific asthma therapy are given.
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Human eosinophils: their accumulation, activation and fate.
TL;DR: This review will summarize some of the knowledge regarding the mechanisms responsible for the accumulation, activation and fate of the eosinophil.
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Production of IL-5 and granulocyte-macrophage colony-stimulating factor by naive human mast cells activated by high-affinity IgE receptor ligation
Robert B. Bressler,John G. Lesko,Margaret L. Jones,Matthew W Wasserman,R Dickason,Marilyn M. Huston,Susan W. Cook,David P. Huston +7 more
TL;DR: It is demonstrated that naive mast cells do not constitutively produce IL-5 or GM-CSF protein but are a major source of these eosinophilotropic cytokines on high-affinity IgE receptor ligation.
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