Apoptotic cells promote macrophage survival by releasing the antiapoptotic mediator sphingosine-1-phosphate.

نویسندگان

  • Andreas Weigert
  • Axel M Johann
  • Andreas von Knethen
  • Helmut Schmidt
  • Gerd Geisslinger
  • Bernhard Brüne
چکیده

Programmed cell death is vital for a number of pathophysiologic settings. Apoptotic cells are rapidly engulfed by phagocytes (ie, macrophages), which in turn acquire an anti-inflammatory phenotype known as alternative activation or the M2-type. Here we show that interaction of apoptotic cells with macrophages attenuates cell death pathways in the latter. Protection of human macrophages required phosphoinositide 3-kinase (PI3K), extracellular signal-regulated kinase 1/2 (ERK1/2), and Ca2+ signaling, and correlated with Bcl-X(L) and Bcl-2 up-regulation as well as Ser136-Bad phosphorylation. Unexpectedly, neither phagocytosis nor binding of apoptotic debris to the phagocyte was necessary to induce protection. Surprisingly, apoptotic cells released sphingosine-1-phosphate (S1P), mainly derived from sphingosine kinase 2, as a survival messenger. This points to an active role of apoptotic cells in preventing cell destruction in their neighborhood, with implications for innate immunity and inflammation.

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عنوان ژورنال:
  • Blood

دوره 108 5  شماره 

صفحات  -

تاریخ انتشار 2006