Annexin 1 Cleavage in Activated Neutrophils

Annexin 1 is an anti-inflammatory protein that plays a key role in innate immunity by modulating the activation of several types of cells, including neutrophils. Here we have developed a cleavage assay using tagged annexin 1 and observed marked activity in the membrane fraction of activated neutroph...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-10, Vol.282 (41), p.29998-30004
Main Authors: Vong, Linda, D'Acquisto, Fulvio, Pederzoli-Ribeil, Magali, Lavagno, Luisa, Flower, Roderick J., Witko-Sarsat, Véronique, Perretti, Mauro
Format: Article
Language:English
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Summary:Annexin 1 is an anti-inflammatory protein that plays a key role in innate immunity by modulating the activation of several types of cells, including neutrophils. Here we have developed a cleavage assay using tagged annexin 1 and observed marked activity in the membrane fraction of activated neutrophils. A combination of inhibitors, transfected cells, and proteomic analyses allowed us to identify proteinase 3 as the main enzyme responsible for this cleavage in the N terminus region of the protein, at least in the context of neutrophil activation. Because annexin 1 is an important endogenous anti-inflammatory mediator, blocking its cleavage by proteinase 3 would augment its homeostatic pro-resolving actions and could represent an opportunity for innovative anti-inflammatory drug discovery.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M702876200