Neutrophil apoptosis and hypoxia.
Neutrophils are the most abundant population of leukocytes, which constitute the defense against pathogens. Released by neutrophils the proteolytic enzymes and reactive oxygen species help in eliminating infections, but also cause extensive tissue damage. Neutrophil apoptosis plays an essential role in cell homeostasis and resolution of inflammation. It is mediated by a complex network of intracellular apoptotic/survival signaling pathways and can be modulated by a variety of extracellular stimuli such as hypoxia. Here, we review recent studies on the mechanisms of neutrophil death and survival accentuating on neutrophil apoptosis under hypoxic conditions. Neutrophils possess components of both extrinsic and intrinsic apoptotic routes. However in neutrophils this mechanism has special features. The involvement of death receptors, caspases, mitochondria, and Bcl-2 proteins are discussed. Both the transcription factor NF-kappaB and p38MAPK regulate the neutrophil apoptotic program. Despite that reactive oxygen species (ROS) can directly promote and/or adjust apoptosis, there is no consensus about the role of ROS on neutrophil lifespan. Thus both the type of ROS involved and the site of their generation may be important for neutrophil apoptosis. Finally, hypoxia can activate several signaling pathways. The possible differences between the effects of sustained and intermittent hypoxia are also addressed.
Technion-Israel Institute of technology, Haifa, Israel. larissa@tx.technion.ac.il
L
L
Dyugovskaya
A
A
Polyakov
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000201:enzymology / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases