title: Control of eosinophil toxicity in the lung.
abstract: The inappropriate accumulation of eosinophils and the subsequent release of their potent pro-inflammatory mediator arsenal are thought to be important contributors to the pathogenesis of asthma and other allergic diseases. It is also becoming apparent that eosinophils may play a role in the orchestration of immune responses in the asthmatic lung. There is therefore much interest in the development of strategies to limit or prevent eosinophil-induced toxicity. The mechanisms by which eosinophils accumulate in the peribronchial tissues of the lung are complex and include enhanced differentiation and release from the bone marrow, selective adhesion and transendothelial migration, directed movement in response to specific chemotactic mediators and finally prolonged survival as a consequence of delayed apoptosis. Thus it can be appreciated that there are many points at which the toxicity of eosinophils can be limited or even prevented. Important areas for potential advances in glucocorticoid (GC) development include efforts to dissociate their anti-inflammatory effects from unwanted side effects. Other areas include the development of humanized monoclonal antibodies against IL-4, IL-13 and IL-5 together with the inhibition of adhesion pathways and/or chemokines responsible for eosinophil accumulation in the asthmatic lung. Several avenues of research are currently underway in an attempt to define mechanisms by which pro-inflammatory cells such as eosinophils can be safely removed from the asthmatic lung through apoptosis induction and their subsequent ingestion by phagocytes. This review will discuss both the potential and shortcomings of these diverse approaches to limit eosinophil toxicity in the asthmatic lung.
authors.affiliation: Allergic and Asthmatic Inflammation Group, School of Medicine, University of Aberdeen, Scotland, UK. g.m.walsh@abdn.ac.uk
authors.forename: G M
authors.initials: GM
authors.lastname: Walsh
authors.forename: M
authors.initials: M
authors.lastname: Al-Rabia
authors.forename: M G
authors.initials: MG
authors.lastname: Blaylock
authors.forename: D W
authors.initials: DW
authors.lastname: Sexton
authors.forename: C J A
authors.initials: CJ
authors.lastname: Duncan
authors.forename: A
authors.initials: A
authors.lastname: Lawrie
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D001249:Asthma / Q000188:drug therapy / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000502:physiology; D004804:Eosinophils / Q000473:pathology / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000473:pathology / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology
chemical_list: D018927:Anti-Asthmatic Agents; C515456:CCL11 protein, human; D015815:Cell Adhesion Molecules; D054413:Chemokine CCL11; D019742:Chemokines, CC