Eosinophil influx

Various studies have also examined animal models of pulmonary inflammation that are representative of primary eosinophil or neutrophil infiltration. Lung inflammation characterized by eosinophil influx has been used as a model of asthma and is not generally associated with lung fibrosis. After several episodes of repeated antigen challange, a subset of Ascaris -sensitive Cynomolgus monkeys developed a persistent eosinophilia and enhanced intercellular adhesion molecule-1 (ICAM-1) expression on pulmonary endothelial and epithelial cells when compared to control animals (Gundel etal., 1991, 1992). 

Consequently, Zyflo was thoroughly evaluated in a number of clinical trials for effects on models of asthma and in the treatment of chronic asthma. Challenge models of asthma with a variety of stimuli (allergen, exercise, cold dry air, or aspirin) were successful. Results in aspirin-induced asthma were dramatically effective, indicating that leukotrienes are the primary mediators of this response. Zyflo also shows remarkable anti-inflammatory effects, as predicted from animal studies (137). Eosinophil influx and albumin leakage were reduced and the urinary increase in LTE, was blocked (86%)(141,142). 

Elevated eosinophil counts have consistently been shown in the airways in asthma both at baseline and after segmental allergen challenge, and eosinophil influx has been closely related to the late phase bronchoconstrictor response (21). Eosinophils have been closely associated with the degree of airway inflammation, epithelial damage, and disease severity in asthma as confirmed by eosinophil counts in the airway lumen, mucosal tissue, and induced sputum (38) IL-3, IL-5, and GM-CSF release has been shown to prolong airway eosinophil survival by inhibiting apoptosis and to prime eosinophils for mediator release (39). 

Louahed J, Zhou Y, Maloy WL, Rani PU, et al. 2001. Interleukin 9 promotes influx and local maturation of eosinophils. Blood. 97 1035-1042. 

Allergic asthma patients have higher blood levels of NGF. The influx of inflammatory cells in lungs is observed as the neurotrophin expression is augmented. Multiple targets may be affected by neurotrophins as they play a role in allergic inflammation, which include recruitment, maintenance and activation of mast cells and eosinophils and facilitation of TH2 response. Whether neurotrophins can alter TH1/TH2 balance in humans has not yet been established. 

Type III reactions are the result of antigen-antibody (IgG) complexes that accumulate in tissues or the circulation, activate macrophages and the complement system, and trigger the influx of neutrophils, eosinophils, and lymphocytes (inflam-... 

Charlesworth, E.N., Kagey Sobotka, A., Schleimer, RP., Norman, P.S. and Lichtenstein, L.M. (1991). Prednisone inhibits the appearance of inflammatory mediators and the influx of eosinophils and basophils associated with the cutaneous late-phase response to allergen. J. Immunol. 146, 671-676. 

Under normal conditions, the alveolar epithelial and endothelial cell layers that make up the air-blood barrier control the passage of fluids and cells between the air spaces of the lung and the interstitium. Damage to this delicate barrier can cause an inflammatory response and the impairment of lung function. Changes in the permeability of the alveolarcapillary barrier lead to an infusion of proteinaceous serous fluid (edema) and blood cells (neutrophils, macrophages, and eosinophils). This influx of cells usually peaks within the first 3-7 days of the inflammatory response. If the inflammation is sustained it is... 

Repeated exposure of sensitized mice to nebulized OVA (OVA mice) without SEB contact induced bronchial inflammation characterized by mainly eosinophils in the BAL fluid and influx of inflammatory cells in bronchial tissue, as illustrated on hematoxylin-and-eosin-stained sections. When SEB was administered onto the nasal mucosa during the development of bronchial allergic inflammation in response to OVA inhalation, bronchial inflammation was clearly aggravated. Compared to nasal application of SEB in OVA mice, bronchial administration of SEB in OVA mice equally aggravated the inflammatory response in the lower airways. Thus, in bronchial tissue of OVA mice, the inflammatory response was aggravated by SEB contact via the nose and the bronchi. 

HETE, and leukotriene in combination with increases in capillary permeability induced by other mediators such as histamine, the leukotrienes, and PAF leads to the influx of inflammatory cells (neutrophils, eosinophils, and macrophages) into the lung. These elicited cells may then be direct contributors to the secondary inflammatory response often associated with an attack of allergic asthma. 

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