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Opposing regulation of neutrophil apoptosis through the formyl peptide receptor‐like 1/lipoxin A 4 receptor: implications for resolution of inflammation
Author(s) -
El Kebir Driss,
József Levente,
Filep János G.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1107765
Subject(s) - lipoxin , formyl peptide receptor , inflammation , biology , annexin a1 , innate immune system , receptor , microbiology and biotechnology , annexin , apoptosis , serum amyloid a , signal transduction , immunology , programmed cell death , chemotaxis , biochemistry
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 (LXA 4 ) receptor that binds a variety of ligands, including the acute‐phase reactant serum amyloid A (SAA), the anti‐inflammatory lipids LXA 4 and aspirin‐triggered 15‐epi‐LXA 4 (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.