Phagocytosis of cells dying through autophagy evokes a pro-inflammatory response in macrophages.

Abstract:

:Autophagy as a natural part of cellular homeostasis usually takes place unnoticed by neighboring cells. However, its co-occurrence with cell death may contribute to the clearance of these dying cells by recruited phagocytes. Autophagy associated with programmed cell death has recently been reported to be essential for presentation of phoshatidylserine (PS) on the cell surface (Qu et al. 2007) that has a key role in the clearance of apoptotic cells. Recently, we have demonstrated that upon triggering cell death by autophagy in MCF-7 cells, the corpses were efficiently phagocytosed by both human macrophages and non-dying MCF-7 cells. Death as well as engulfment could be prevented by inhibiting autophagy. Based on our data, two molecular mechanisms have been proposed for the uptake of cells which die through autophagy: a PS-dependent pathway which was exclusively used by the living MCF-7 cells acting as non-professional phagocytes, and a PS-independent uptake mechanism that was active in macrophages acting as professional phagocytes. Several lines of evidence suggest that macrophages utilize calreticulin-mediated recognition, tethering, tickling and engulfment processes. Phagocytic uptake of cells dying through autophagy by macrophages leads to a pro-inflammatory response characterized by the induction and secretion of IL-6, TNFalpha, IL-8 and IL-10.

journal_name

Autophagy

journal_title

Autophagy

authors

Petrovski G,Zahuczky G,Májai G,Fésüs L

doi

10.4161/auto.4731

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

509-11

issue

5

eissn

1554-8627

issn

1554-8635

pii

4731

journal_volume

3

pub_type

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