Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal.
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.
Lauber
Kirsten
K
Department of Internal Medicine I, University of Tübingen, Tübingen, Germany.
Bohn
Erwin
E
Kröber
Stefan Martin
SM
Xiao
Yi-jin
YJ
Blumenthal
Sibylle G
SG
Lindemann
Ralph K
RK
Marini
Patrizia
P
Wiedig
Carolin
C
Zobywalski
Anke
A
Baksh
Shairaz
S
Xu
Yan
Y
Autenrieth
Ingo B
IB
Schulze-Osthoff
Klaus
K
Belka
Claus
C
Stuhler
Gernot
G
Wesselborg
Sebastian
S
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
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