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Targeting Neutrophil Apoptosis for Enhancing the Resolution of Inflammation
Department of Pathology and Cell Biology, University of Montreal and Research Center, Maisonneuve-Rosemont Hospital, 5415 Boulevard de l'Assomption, Montreal, QC H1T 2M4, Canada
* Author to whom correspondence should be addressed.
Received: 15 April 2013; in revised form: 25 April 2013 / Accepted: 14 May 2013 / Published: 22 May 2013
(This article belongs to the Special Issue Apoptosis
Abstract: Resolution of acute inflammation is an active process that requires inhibition of further leukocyte recruitment and removal of leukocytes from inflamed sites. Emigrated neutrophils undergo apoptosis before being removed by scavenger macrophages. Recent studies using a variety of gene knockout, transgenic and pharmacological strategies in diverse models of inflammation established neutrophil apoptosis as a critical control point in resolving inflammation. Analysis of death mechanisms revealed distinct features in executing the death program in neutrophils, which can be exploited as targets for controlling the lifespan of neutrophils. Indeed, anti-inflammatory and pro-resolution lipid mediators derived from essential fatty acids, such as lipoxin A4 and resolvin E1, autacoids and proteins, such as annexin A1 and TRAIL, and cyclin-dependent kinase inhibitors, can enhance the resolution of inflammation through induction of neutrophil apoptosis and promoting their removal by efferocytosis. In this review, we discuss recent advances in understanding the molecular basis of these actions, highlighting the potential of therapeutic induction of neutrophil apoptosis for dampening neutrophil-mediated tissue injury and inflammation underlying a variety of diseases.
Keywords: neutrophils; apoptosis; phagocytosis; lipoxins; resolvins; annexin A1; TRAIL; cyclin-dependent kinases; Mcl-1; resolution of inflammation
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MDPI and ACS Style
El Kebir, D.; Filep, J.G. Targeting Neutrophil Apoptosis for Enhancing the Resolution of Inflammation. Cells 2013, 2, 330-348.
El Kebir D, Filep JG. Targeting Neutrophil Apoptosis for Enhancing the Resolution of Inflammation. Cells. 2013; 2(2):330-348.
El Kebir, Driss; Filep, János G. 2013. "Targeting Neutrophil Apoptosis for Enhancing the Resolution of Inflammation." Cells 2, no. 2: 330-348.