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    Proteinase 3 hitches a ride with microvesicles to perpetuate inflammation

    Team Veronique Witko-Sarsat & Luc Mouthon

    Microvesicles (MVs) are tiny vesicles generated from circulating leukocytes or endothelial cells which can circulate and disseminate throughout the body, carrying with them various associated molecules and they can be involved in inflammation and also vascular injury. MVs are surrounded by a membrane containing high levels of phosphatidylserine, a lipid that is normally located inside the cell.

     The team of Véronique Witko-Sarsat at the Cochin Institute, in collaboration with the team of Chantal Boulanger at the PAARC in Paris, have demonstrated in a study published in "The Journal of Biological Chemistry" that the proteinase 3, a protease found in neutrophils, can stick to circulating microvesicles and transfer a new pro-inflammatory property to the vesicles.  The binding of proteinase 3 occurred specifically on the phosphatidylserine expressed at the membrane and this was because this protease possessed a peculiar "sticky patch" allowing the recognition of the lipid. In addition, proteinase 3 is known as the autoantigen in autoimmune vasculitis and by traveling throughout the body on microvesicles, it could contribute to the pathogenesis of this disease.

     This work has underscored a novel pathway by which the autoantigen, PR3 tightly bound to microvesicles, could transit and promote an immune response. 


    Learn more:

    Proteinase 3 is a phosphatidylserine binding protein which affects the production and function of microvesicles. Martin KR, Kantari-Mimoun C, Yin M, Pederzoli-Ribeil M, Angelot-Delettre F, Ceroi A, Grauffel C, Benhamou M, Reuter N, Saas P, Frachet P, Boulanger CM, Witko-Sarsat V. J Biol Chem. 2016 Mar 9. pii: jbc.M115.698639


    Resarcher contact:

    Véronique Witko-Sarsat
    Institut Cochin (CNRS UMR8104, Inserm U1016, Université Paris Descartes)
    22 rue Méchain, 75014 Paris – France
    33(0)1 40 51 66 56


    Figure legend:

    Computational model of membrane-associated proteinase 3 from molecular dynamics simulations. The phosphatidylserine-specific binding site is represented with green spheres, the proteinase 3 with green cartoons, the hydrophobic region of the membrane is represented using a gold surface while the hydrophilic phosphate and PS head groups are shown with cyan sticks.

    The image was prepared by Cedric Grauffel and Nathalie Reuter (University of Bergen, Norway) using Pymol.