Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease.
Neutrophils are the most abundant cell type involved in the innate immune response. They are rapidly recruited to sites of injury or infection where they engulf and kill invading microorganisms. Neutrophil apoptosis, the process of programmed cell death that prevents the release of neutrophil histotoxic contents, is tightly regulated and limits the destructive capacity of neutrophil products to surrounding tissue. The subsequent recognition and phagocytosis of apoptotic cells by phagocytic cells such as macrophages is central to the successful resolution of an inflammatory response and it is increasingly apparent that the dying neutrophil itself exerts an anti-inflammatory effect through modulation of surrounding cell responses, particularly macrophage inflammatory cytokine release. Apoptosis may be delayed, induced or enhanced by micro-organisms dependent on their immune evasion strategies and the health of the host they encounter. There is now an established field of research aimed at understanding the regulation of apoptosis and its potential as a target for therapeutic intervention in inflammatory and infective diseases. This review focuses on the physiological regulation of neutrophil apoptosis with respect to the innate immune system and highlights recent advances in mechanistic understanding of apoptotic pathways and their therapeutic manipulation in appropriate and excessive innate immune responses.
Fox
Sarah
S
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, Edinburgh, UK. sfox1 @ staffmail.ed.ac.uk
Leitch
Andrew E
AE
Duffin
Rodger
R
Haslett
Christopher
C
Rossi
Adriano G
AG
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy; D007249:Inflammation; D008262:Macrophage Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology