Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal

被引:741
作者
Lauber, K
Bohn, E
Kröber, SM
Xiao, YJ
Blumenthal, SG
Lindemann, RK
Marini, P
Wiedig, C
Zobywalski, A
Baksh, S
Xu, Y
Autenrieth, IB
Schulze-Osthoff, K
Belka, C
Stuhler, G
Wesselborg, S [1 ]
机构
[1] Univ Tubingen, Dept Internal Med 1, D-72074 Tubingen, Germany
[2] Univ Tubingen, Inst Med Microbiol, D-72074 Tubingen, Germany
[3] Univ Tubingen, Inst Pathol, D-72074 Tubingen, Germany
[4] Cleveland Clin Fdn, Dept Canc Biol, Cleveland, OH 44195 USA
[5] Cleveland Clin Fdn, Dept Gynecol & Obstet, Cleveland, OH 44195 USA
[6] Univ Tubingen, Dept Radiat Oncol, D-72074 Tubingen, Germany
[7] Univ Tubingen, Dept Internal Med 2, D-72074 Tubingen, Germany
[8] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Med, Boston, MA 02115 USA
[9] Univ Dusseldorf, Inst Mol Med, D-4000 Dusseldorf, Germany
关键词
D O I
10.1016/S0092-8674(03)00422-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:717 / 730
页数:14
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