Airway inflammation eosinophils

Humbles AA, Lu B, Friend DS, et al. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci U S A 2002 99(3) 1479-1484. 

Lukacs NW, Standiford TJ, Chensue SW, Kunkel RG, Stricter RM, Kunkel SL. C-C chemokine-induced eosinophil chemotaxis during allergic airway inflammation. J Leukoc Biol 1996 60(5) 573-578. 

Lukacs, N.W., Stricter, R.M., Chensue, S.W., Widmer, M. and Kunkel, S.L. (1995) TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation. Journal of Immunology 154, 5411-5417. 

Asthma is characterized by variable symptoms such as wheeze, shortness of breath and coughing and is usually associated with airway inflammation, with variably reduced spirometric indices [4, 5], with increased non-specific airway responsiveness (AR) to spasmogens [6, 7] and increased levels of semm immunoglobulin E (IgE) and eosinophils [8-10]. The symptoms of asthma are primarily due to excessive airway narrowing, which leads to an increased resistance to airflow, especially during forced expiration, and produces characteristic spirometric findings. A cardinal feature of asthma is that airway narrowing is reversible either spontaneously or as the result of therapy. 

At the cellular level, eosinophils, mast cells, alveolar macrophages, lymphocytes and neutrophils recruited to the airways of asthmatics produce a variety of inflammatory mediators, such as histamine, kinins, neuropeptides, and leukotrienes, which lead to airway smooth muscle constriction and obstruction of airflow, and the perpetuation of airway inflammation [20, 21]. An understanding of the inflammatory processes and the molecular pathways of these mediators has led to the development and widespread use of several pharmacologic agents that mitigate airway inflammation and bronchoconstriction. 

The latest studies show that reactive nitrogen species play even more important role in asthma development. It was found that exhaled nitrogen oxide, an indicator of eosinophilic airway inflammation, is drastically enhanced in asthmatic patients. Correspondingly, it has been shown that lung damage is characterized by the augmentation of nitrotyrosine and iNOS expression in neutrophils, eosinophils, and macrophages in the airways of asthmatic patients [266],... 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

Hellings PW, Vandenberghe P, Kasran A, Coorevits L, Overbergh L, Mathieu C, et al Blockade of CTLA-4 enhances allergic sensitization and eosinophilic airway inflammation in genetically predisposed mice. Eur J Immunol 2002 32 585-594. 

Lambrecht BN. Salomon B. Klatzmann D. Pauwels RA Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol 1998 160 4090-4097. 

Lee YL, Fu CL, Ye YL, Chiang BL Administration of interleukin-12 prevents mite Der p 1 allergen-IgE antibody production and airway eosinophil infiltration in an animal model of airway inflammation. Scand J Immunol 1999 49 229-236. 

Th2 cytokine IL-10 is an antiinflammatory cytokine that suppresses the secretion of proinflammatory cytokines (Dll), allergen-induced airway inflammation, and nonspecific airway responsiveness (T9). IL-13 shares a receptor component, signaling pathways, and many biological activities with IL-4. In fact, IL-13 is also an antiinflammatory cytokine and plays a unique role in the optimal induction and maintenance of IgE production and IgE-mediated allergic responses when IL-4 production is low or absent (DIO, W12). Moreover, IL-13 or IL-4 shows a synergistic effect with TNF-a or IL-5 on eosinophil activation (L20). Recently, IL-11 was found to be involved in the chronic remodeling seen in asthmatic airways and is associated with increasing severity of the disease (Ml6). 

Macrophage inflammatory protein-1 alpha influences eosinophil recruitment in antigen-specific airway inflammation. Eur. J. Immunol. 25, 245-251. 

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