Inflammation Eosinophils

Whilst eosinophils appear unimportant in the induction of protective responses to GI helminths, they are present in large numbers in the inflamed gut and it has therefore been suggested that they play a part in the induction of enteropathy. Moreover, eosinophils have been implicated in the induction of intestinal inflammation eosinophilic gastroenteritis, ulcerative colitis and Crohn s disease. However, IL-5-deficient mice, or GM-CSF transgenic mice (which typically have a blood eosinophilia of approximately 25%) infected with T. spiralis did not show a significant exacerbation or amelioration of either protective or pathological responses (C.E. Lawrence, unpublished observation). 

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

Inflammation is present in the lungs of all smokers. It is unclear why only 15% to 20% of smokers develop COPD, but susceptible individuals appear to have an exaggerated inflammatory response.5 O The inflammation of COPD differs from that seen in asthma, so the use of anti-inflammatory medications and the response to those medications are different. The inflammation of asthma is mainly mediated through eosinophils and mast cells. In COPD the primary inflammatory cells include neutrophils, macrophages, and CD8+ T lymphocytes. 

Eosinophils may be increased in some patients, particularly during exacerbations. Activated inflammatory cells release a variety of mediators, most notably leukotriene B4, interleukin-8, and tumor necrosis factor-a (TNF-a). Various proteinases, such as elastase, cathepsin G, and proteinase-3, are secreted by activated neutrophils. These mediators and proteinases are capable of sustaining inflammation and damaging lung structures. 

Key Words Allergy asthma lung pulmonary T cell mast cell eosinophil inflammation dendritic cell IgE B cell. 

Ravensberg AJ, Ricciardolo EL, van Schadewijk A, et al. Eotaxin-2 and eotaxin-3 expression is associated with persistent eosinophilic bronchial inflammation in patients with asthma after allergen challenge. J Allergy Clin Immunol 2005 115(4) 779-785. 

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. 

Bousquet J, Chanez P, Vignola AM, Lacoste JY, Michel FB. Eosinophil inflammation in asthma. Am J Respir Crit Care Med 1994 150 S33-38. 

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],... 

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