title: Appetizing rancidity of apoptotic cells for macrophages: oxidation, externalization, and recognition of phosphatidylserine.
abstract: Programmed cell death (apoptosis) functions as a mechanism to eliminate unwanted or irreparably damaged cells ultimately leading to their orderly phagocytosis in the absence of calamitous inflammatory responses. Recent studies have demonstrated that the generation of free radical intermediates and subsequent oxidative stress are implicated as part of the apoptotic execution process. Oxidative stress may simply be an unavoidable yet trivial byproduct of the apoptotic machinery; alternatively, intermediates or products of oxidative stress may act as essential signals for the execution of the apoptotic program. This review is focused on the specific role of oxidative stress in apoptotic signaling, which is realized via phosphatidylserine-dependent pathways leading to recognition of apoptotic cells and their effective clearance. In particular, the mechanisms involved in selective phosphatidylserine oxidation in the plasma membrane during apoptosis and its association with disturbances of phospholipid asymmetry leading to phosphatidylserine externalization and recognition by macrophage receptors are at the center of our discussion. The putative importance of this oxidative phosphatidylserine signaling in lung physiology and disease are also discussed.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA. kagan@pitt.edu
authors.forename: V E
authors.initials: VE
authors.lastname: Kagan
authors.forename: G G
authors.initials: GG
authors.lastname: Borisenko
authors.forename: B F
authors.initials: BF
authors.lastname: Serinkan
authors.forename: Y Y
authors.initials: YY
authors.lastname: Tyurina
authors.forename: V A
authors.initials: VA
authors.lastname: Tyurin
authors.forename: J
authors.initials: J
authors.lastname: Jiang
authors.forename: S X
authors.initials: SX
authors.lastname: Liu
authors.forename: A A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: J P
authors.initials: JP
authors.lastname: Fabisiak
authors.forename: W
authors.initials: W
authors.lastname: Uthaisang
authors.forename: B
authors.initials: B
authors.lastname: Fadeel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000276:immunology; D010718:Phosphatidylserines / Q000378:metabolism*
chemical_list: D010718:Phosphatidylserines