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Defining a role for platelets in allergic inflammation
1Leukocyte Biology Section, National Heart and Lung Institute, Imperial College, London SW7 2AZ, U.K. s.pitchford@imperial.ac.uk
Abstract:
There is now considerable evidence suggesting a role for platelets as inflammatory cells. These actions are distinct from their classically known actions performed during thrombosis and haemostasis, and include the expression of adhesion molecules and contact-dependent activation of leucocytes, the release of a plethora of inflammatory mediators, activation in cells of the adaptive immune response and the ability to migrate and undergo chemotaxis. Chronic asthma is a disease characterized by a mixed inflammatory cell pulmonary infiltrate, AHR (airways hyper-responsiveness) and tissue remodelling. Clinical data from patients suffering from asthma, allergic rhinitis and allergic dermatitis reveal changes in platelet behaviour and function during or after allergen exposure. Furthermore, mouse models of allergic inflammation demonstrate a role for intact platelets in eosinophil and lymphocyte recruitment to the lungs, a mechanism that is P-selectin (platelet selectin)-dependent. Models of chronic inflammation also reveal the participation of platelets in tissue remodelling events whereby platelet depletion was found to be more effective in suppressing airway remodelling processes than the administration of a glucocorticosteroid. This process of destruction and repair to the architecture of airway tissue is therefore perhaps enhanced by platelet activation. Recent evidence demonstrates that platelets can undergo chemotaxis and indicates an ability to migrate through inflamed tissue, where they localize to specific tissue sites. Indeed, platelets have been shown to become activated and recruited to various body compartments in direct response to allergen via IgE and this is suggestive of a link between the innate and adaptive immune responses. Thus these actions may lead to pathophysiological events that alter disease progression, since platelet depletion suppresses AHR in allergic rabbits. Further investigations into the role of platelets in inflammation may be beneficial in the search for future therapeutic targets in the treatment of asthma and allergy.
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