Allergic airway inflammation eosinophil role

Fulkerson, P.C., Fischetti, C.A., McBride, M.L., Hassman, L.M., Hogan, S.P. etal. (2006) A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation. Proceedings of the National Academy of Sciences of the United States of America, 103, 16418-16423. 

Conroy, D. M., Humbles, A. A., Rankin, S. M., Palframan, R. T., Collins, P. D., Griffiths-Johnson, D. A., Jose, P. J., and Williams, T. J. (1997) The role of the eosinophil-selective chemokines, eotaxin, in allergic and non-allergic airways inflammation, in New Perspectives in Eosinophils. Role in Inflammation Associated with Allergy, Asthma and Parasitic Disease (Cordeiro, R., Moqbel, R., and Weller, P. F., eds.), Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil, pp. 183-191. 

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). 

The progression of airway inflammations involves several types of cells such as CD4", Th2 cells, eosinophils, and mast cells (Wills-Karp, 1999). The immunopathogenic role of Th2 cells is determined by the roles of their products, such as IL-4, IL-5, and IL-13 in the recruitment and activation of the primary effector cells of the allergic response, eosinophils, and mast cells. Activation of these cells results in the release of many inflammatory mediators that seem to induce AHR individually or coordinately (Drazen et ah, 1996 Galli, 1997), although the precise molecular mechanisms predisposing to the development of AHR in asthmatics are largely unknown. 

Other CC chemokines are likely also important in the development of eosinophilic airway inflammation. MCP-3 (MARC/FIC) was originally isolated from mast cells, which would immediately center a role for this eosinophil chemoattractant on early allergic responses. Depletion of MCP-3 in allergic airway models has demonstrated a significant role for this molecule on eosinophil recruitment to the airways (39). In addition, studies in our own laboratory examining the role of other CC chemokines, specifically MIP-la, have demonstrated that it is not only important in mononuclear recruitment... 

Bronchial biopsies in stable atopic asthmatics have observed these components (19,64). Several Th2-type cytokines, (IL-4, IL-5, IL-13, but not JFNy) and C-C chemokines are produced by multiple cells types, which regulate IgE synthesis and lead to the generation of eosinophilic airway inflammation (Fig. 9) (321). Allergic tissue damage results from the release of basic proteins, leukotrienes, and PAF secreted by activated eosinophils. It is clear that the mast cell plays an important role in the immediate response and that T cells play a key role in orchestrating the nature and severity of the inflammation by the secretion of cytokines. As stated earlier, the eosinophil is regarded as the primary effector cell due to the capacity to secrete major basic protein and eosinophil cationic protein, which have profound cytotoxic effects on the airway epithelium (316). 

Th2-type cytokines such as IL-4, IL-5, and IL-13 orchestrate a cascade of events during development of an allergic inflammatory response. This is demonstrated both clinically and in preclinical animal models (404, 405). IL-4 plays a critical role in the early commitment of ThO cells to Th2 cells and regulates IgE secretion by B-cells. It also induces V-CAM expression on endothelial cells, promotes eosinophilic inflammation, and increases airway mucus production. 

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