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Published online before print May 21, 2008

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(Journal of Leukocyte Biology. 2008;84:600-606.)
© 2008 by Society for Leukocyte Biology

Opposing regulation of neutrophil apoptosis through the formyl peptide receptor-like 1/lipoxin A₄ receptor: implications for resolution of inflammation

Research Center, Maisonneuve-Rosemont Hospital and Department of Pathology and Cell Biology, University of Montréal, Montréal, Quebec, Canada

¹ Correspondence: Research Center, Maisonneuve-Rosemont Hospital, 5415 Boulevard de l’Assomption, Montréal, QC, Canada, H1T 2M4. E-mail: janos.g.filep{at}umontreal.ca

ABSTRACT

Neutrophils have a central role in innate immunity, and their programmed cell death and removal are critical to the optimal expression as well as to efficient resolution of inflammation. Human neutrophils express the pleiotropic receptor formyl peptide receptor-like 1/lipoxin A4 (LXA₄) receptor that binds a variety of ligands, including the acute-phase reactant serum amyloid A (SAA), the anti-inflammatory lipids LXA₄ and aspirin-triggered 15-epi-LXA₄ (ATL), and the glucocorticoid-inducible protein annexin 1. In addition to regulation of neutrophil activation and recruitment, these ligands have a profound influence on neutrophil survival and apoptosis with contrasting actions, mediating aggravation or resolution of the inflammatory response. Thus, annexin 1 accelerates, whereas SAA rescues human neutrophils from constitutive apoptosis by preventing mitochondrial dysfunction and subsequent activation of caspase-3. Furthermore, ATL overcomes the antiapoptosis signal from SAA and redirects neutrophils to caspase-mediated cell death. We review recent developments about the molecular basis of these actions and suggest a novel mechanism by which aspirin promotes resolution of acute inflammation and tissue injury.

Key Words: acute-phase reactants • lipid mediators