Neutrophil apoptosis: a target for enhancing the resolution of inflammation.
Neutrophils are essential for host defense and their programmed cell death and removal are critical for the optimal expression as well as for efficient resolution of inflammation. Delayed neutrophil apoptosis or impaired clearance of apoptotic neutrophils by macrophages contributes to the progression of chronic inflammation. Under most conditions, neutrophils are exposed to multiple factors and their fate would ultimately depend on the balance between pro-survival and pro-apoptotic signals. Life or death decisions are tightly controlled by a complex network of intracellular signaling pathways. Accumulating data indicate that receptors, such as the formyl peptide receptor 2/lipoxin receptor or beta(2)-integrins can generate contrasting cues in neutrophils in a ligand-specific manner and suggest a hierarchy among these signals. In this article, we review recent advances on how pro-apoptosis and pro-survival signals interact to determine the fate of neutrophils and the inflammatory response, and highlight novel pharmacological strategies that could be used to enhance the resolution of inflammation by redirecting neutrophils to apoptosis.
Filep
János G
JG
Research Center, Maisonneuve-Rosemont Hospital, Department of Pathology and Cell Biology, University of Montréal, Montréal, Québec, Canada. janos.g.filep@umontreal.ca
El Kebir
Driss
D
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018821:CD18 Antigens / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology* / Q000503:physiopathology; D008024:Ligands; D051379:Mice; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D018821:CD18 Antigens; C105101:FPR2 protein, human; D008024:Ligands; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D018844:Cyclin-Dependent Kinases