Key mechanisms governing resolution of lung inflammation.
Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered.
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
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Robb
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
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Regan
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
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Dorward
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. a.g.rossi@ed.ac.uk.
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Rossi
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
D016207:Cytokines; D018836:Inflammation Mediators
Apoptosis; ETosis; Efferocytosis; Eosinophils; Lung diseases; Lung inflammation; Macrophages; Neutrophils; Pro-resolution mediators