An apoptosis differentiation programme in human polymorphonuclear leucocytes.
Human PMNs (polymorphonuclear leucocytes or neutrophils) are essential to the innate immune response against bacterial pathogens and are a key part of the acute inflammatory response. Although progress has been made, the molecular basis for termination of inflammation during bacterial infection in humans is largely undefined. To that end, we used genomics strategies to gain new insight into processes that facilitate resolution of neutrophil-mediated inflammation and bacterial infection. On the basis of a series of recent studies, we propose that global changes in PMN gene expression after phagocytosis comprise an apoptosis differentiation programme, which represents the final stage of transcription-regulated PMN maturation. Our studies indicate that the apoptosis differentiation programme regulates multiple post-phagocytic processes in human neutrophils, such as cell fate and proinflammatory activity, and is modulated by PMN-derived reactive oxygen species. Collectively, these studies establish a global model of host cell-pathogen interaction, which provides fundamental insight into the resolution of infection in humans.
Kobayashi
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SD
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA.
Deleo
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FR
D017209:Apoptosis; D002454:Cell Differentiation; D015536:Down-Regulation; D006801:Humans; D007239:Infections; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000382:microbiology / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology; D010587:Phagocytosis; D017382:Reactive Oxygen Species; D014158:Transcription, Genetic
D017382:Reactive Oxygen Species