title: Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal.
abstract: Efficient engulfment of the intact cell corpse is a critical end point of apoptosis, required to prevent secondary necrosis and inflammation. The presentation of "eat-me" signals on the dying cell is an important part of this process of recognition and engulfment by professional phagocytes. Here, we present evidence that apoptotic cells secrete chemotactic factor(s) that stimulate the attraction of monocytic cells and primary macrophages. The activation of caspase-3 in the apoptotic cell was found to be required for the release of this chemotactic factor(s). The putative chemoattractant was identified as the phospholipid, lysophosphatidylcholine. Further analysis showed that lysophosphatidylcholine was released from apoptotic cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A(2). These data suggest that in addition to eat-me signals, apoptotic cells display attraction signals to ensure the efficient removal of apoptotic cells and prevent postapoptotic necrosis.
authors.affiliation: Department of Internal Medicine I, University of Tübingen, Tübingen, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.forename: Erwin
authors.initials: E
authors.lastname: Bohn
authors.forename: Stefan Martin
authors.initials: SM
authors.lastname: Kröber
authors.forename: Yi-jin
authors.initials: YJ
authors.lastname: Xiao
authors.forename: Sibylle G
authors.initials: SG
authors.lastname: Blumenthal
authors.forename: Ralph K
authors.initials: RK
authors.lastname: Lindemann
authors.forename: Patrizia
authors.initials: P
authors.lastname: Marini
authors.forename: Carolin
authors.initials: C
authors.lastname: Wiedig
authors.forename: Anke
authors.initials: A
authors.lastname: Zobywalski
authors.forename: Shairaz
authors.initials: S
authors.lastname: Baksh
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
authors.forename: Gernot
authors.initials: G
authors.lastname: Stuhler
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wesselborg
mesh_terms: D000818:Animals; D017089:Ankyrin Repeat / Q000235:genetics; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D022081:Cell Surface Extensions / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000201:enzymology* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D050356:Lipid Metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D051379:Mice; D010586:Phagocytes / Q000201:enzymology* / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D010741:Phospholipases A / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D008244:Lysophosphatidylcholines; D011500:Protein Synthesis Inhibitors; D010741:Phospholipases A; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases