Annexin A2 binds to endosomes following organelle destabilization by particulate wear debris

Department of Pathology, Albert Einstein College of Medicine, New York 10461, USA.
Nature Communications (Impact Factor: 11.47). 03/2012; 3:755. DOI: 10.1038/ncomms1754
Source: PubMed


Endosomal functions are contingent on the integrity of the organelle-limiting membrane, whose disruption induces inflammation and cell death. Here we show that phagocytosis of ultrahigh molecular weight polyethylene particles induces damage to the endosomal-limiting membrane and results in the leakage of cathepsins into the cytosol and NLRP3-inflammasome activation. Annexin A2 recruitment to damaged organelles is shown by two-dimensional DIGE protein profiling, endosomal fractionation, confocal analysis of endogenous and annexin A2-GFP transfected cells, and immunogold labelling. Binding experiments, using fluorescent liposomes, confirms annexin A2 recruitment to endosomes containing phagocytosed polyethylene particles. Finally, an increase in cytosolic cathepsins, NLRP3-inflammasome activation, and IL-1 production is seen in dendritic cells from annexin A2-null mice, following exposure to polyethylene particles. Together, the results indicate a functional role of annexin A2 binding to endosomal membranes following organelle destabilization.

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Available from: Cristina Clement
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    • "Annexin A2 has also been shown to modulate macrophage activation as well [50], [51]. In murine dendritic cells challenged with particulate wear debris, A2 has been shown to stabilize endosomal membrane and inhibits inflammasome activation [52]. We therefore asked whether A2 was involved in IL-1 production in GBM cells. "
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    • "Dendritic cells interact with T and B lymphocytes as well as NK cells to induce and modulate immune responses, including those critically involved in tumor immunosurveillance [37]. Under DAMPs stimuli, such as wear debris from articulating surface, cytosolic ANXA2-S100A10 complex participates in restoring endosomal membrane integrity, thus curtailing NLRP3 inflammasome activation and IL-1 and IL-18 secretion in dendritic cells [38]. It may suggest that, in ANXA2 knockout mice, antigen presenting may be interfered in dendritic cells, thus retarding adaptive immune system activation. "
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