Apoptotic cells as sources for biologically active oxidized phospholipids.
Acute inflammation is characterized by an accumulation of polymorphonuclear cells (PMNs), generation of reactive oxygen species, subsequent apoptosis of PMNs, and finally phagocytosis of apoptotic cells by macrophages. Recently, it has been demonstrated that during apoptosis oxidation of membrane phospholipids, especially phosphatidylserine, occurs. Moreover, we have shown that membrane vesicles released from apoptotic cells contain biologically active oxidized phospholipids. The involvement of oxidized phospholipids in the development of atherosclerosis, which is described as a chronic inflammatory disease, is increasingly recognized. These oxidized phospholipids were shown to induce several proinflammatory genes, such as monocyte chemoattractant protein 1 or interleukin-8, and it is hypothesized that lipid oxidation products also play a role in other chronic inflammatory disorders. On the other hand, oxidized phospholipids were shown to exert antiendotoxin effects by inhibiting lipopolysaccharide-induced signaling, representing a possible feedback loop during gram-negative infection. Additionally, it has been described that oxidized phospholipids are capable of inducing genes such as heme oxygenase-1 that are important for the resolution of acute inflammation. Moreover, oxidized phospholipids serve as recognition signals on apoptotic cells facilitating phagocytosis. In this review, we discuss the hypothesis that oxidized phospholipids generated in apoptotic cells (a) propagate chronic inflammation and (b) contribute to the resolution of acute inflammation.
Kadl
Alexandra
A
Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Bochkov
Valery N
VN
Huber
Joakim
J
Leitinger
Norbert
N
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001161:Arteriosclerosis / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2; D019040:E-Selectin / Q000276:immunology; D042783:Endothelial Cells / Q000378:metabolism; D004731:Endotoxins / Q000276:immunology; D005786:Gene Expression Regulation; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007249:Inflammation / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D019040:E-Selectin; D004731:Endotoxins; D007527:Isoenzymes; D010743:Phospholipids; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases