title: Glucocorticoid-mediated regulation of granulocyte apoptosis and macrophage phagocytosis of apoptotic cells: implications for the resolution of inflammation.
abstract: Glucocorticoids represent one of the most effective clinical treatments for a range of inflammatory conditions, including severe acute inflammation. Although glucocorticoids are known to affect processes involved in the initiation of inflammation, the influence of glucocorticoids on the mechanisms by which acute inflammation normally resolves have received less attention. Apoptosis of granulocytes present at inflamed sites leads to their rapid recognition and internalisation by macrophages, a process which may be important for resolution of inflammation. However, if clearance of either eosinophils or neutrophils is impaired, these cells rapidly undergo secondary necrosis leading to release of pro-inflammatory mediators from the phagocyte, potentially prolonging inflammatory responses. Physiologically relevant concentrations of glucocorticoids accelerate eosinophil apoptosis whilst delaying neutrophil apoptosis during in vitro culture. Here we discuss key pathways regulating the granulocyte apoptotic programme and summarise the effects of glucocorticoids on monocyte differentiation and the consequent changes to apoptotic cell clearance capacity. Definition of the mechanisms underlying resolution of inflammatory responses following glucocorticoid treatment may unveil new targets for modulation of inflammatory disease, allowing co-ordinated augmentation of granulocyte apoptosis together with increased macrophage capacity for clearance of apoptotic cells.
authors.affiliation: MRC Centre for Inflammation Research, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Heasman
authors.forename: K M
authors.initials: KM
authors.lastname: Giles
authors.forename: C
authors.initials: C
authors.lastname: Ward
authors.forename: A G
authors.initials: AG
authors.lastname: Rossi
authors.forename: C
authors.initials: C
authors.lastname: Haslett
authors.forename: I
authors.initials: I
authors.lastname: Dransfield
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D005109:Extracellular Matrix / Q000276:immunology; D005938:Glucocorticoids / Q000627:therapeutic use*; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D016328:NF-kappa B