Author
Listed:
- Brian Scharf
(Albert Einstein College of Medicine)
- Cristina C. Clement
(Albert Einstein College of Medicine)
- Xiao-Xuan Wu
(Montefiore Medical Center)
- Kateryna Morozova
(Albert Einstein College of Medicine)
- Diego Zanolini
(Albert Einstein College of Medicine)
- Antonia Follenzi
(Albert Einstein College of Medicine)
- Jorge N. Larocca
(Albert Einstein College of Medicine)
- Kalle Levon
(NYU-Poly)
- Fayyaz S. Sutterwala
(University of Iowa)
- Jacob Rand
(Albert Einstein College of Medicine
Montefiore Medical Center)
- Neil Cobelli
(Montefiore Medical Center)
- Ed Purdue
(Hospital for Special Surgery)
- Katherine A. Hajjar
(Weill Cornell Medical College)
- Laura Santambrogio
(Albert Einstein College of Medicine
Albert Einstein College of Medicine)
Abstract
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.
Suggested Citation
Brian Scharf & Cristina C. Clement & Xiao-Xuan Wu & Kateryna Morozova & Diego Zanolini & Antonia Follenzi & Jorge N. Larocca & Kalle Levon & Fayyaz S. Sutterwala & Jacob Rand & Neil Cobelli & Ed Purdu, 2012.
"Annexin A2 binds to endosomes following organelle destabilization by particulate wear debris,"
Nature Communications, Nature, vol. 3(1), pages 1-10, January.
Handle:
RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1754
DOI: 10.1038/ncomms1754
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