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Calreticulin (CRT), a protein involved in apoptotic cell recognition, was found to be a new PR3 partner coexpressed with PR3 on the neutrophil plasma membrane during apoptosis, but not after degranulation. The association between PR3 and CRT was demonstrated in neutrophils by confocal microscopy and coimmunoprecipitation. Evidence for a direct interaction between PR3 and the globular domain of CRT, but not with its P domain, was provided by surface plasmon resonance spectroscopy. Phagocytosis of apoptotic neutrophils from healthy donors was decreased after blocking lipoprotein receptor-related protein (LRP), a CRT receptor on macrophages. In contrast, neutrophils from patients with granulomatosis with polyangiitis expressing high membrane PR3 levels showed a lower rate of phagocytosis than those from healthy controls not affected by anti-LRP, suggesting that the LRP-CRT pathway was disturbed by PR3-CRT association. Moreover, phagocytosis of apoptotic PR3-expressing cells potentiated proinflammatory cytokine in vitro by human monocyte-derived macrophages and in vivo by resident murine peritoneal macrophages, and diverted the anti-inflammatory response triggered by the phagocytosis of apoptotic cells after LPS challenge in thioglycolate-elicited murine macrophages. Therefore, membrane PR3 expressed on apoptotic neutrophils might amplify inflammation and promote autoimmunity by affecting the anti-inflammatory \u201creprogramming\u201d of macrophages.<\/jats:p>","DOI":"10.4049\/jimmunol.1200600","type":"journal-article","created":{"date-parts":[[2012,7,29]],"date-time":"2012-07-29T00:52:56Z","timestamp":1343523176000},"page":"2574-2583","source":"Crossref","is-referenced-by-count":71,"title":["Proteinase 3, the Autoantigen in Granulomatosis with Polyangiitis, Associates with Calreticulin on Apoptotic Neutrophils, Impairs Macrophage Phagocytosis, and Promotes Inflammation"],"prefix":"10.1093","volume":"189","author":[{"given":"Julie","family":"Gabillet","sequence":"first","affiliation":[{"name":"INSERM U1016 , Paris 75014,","place":["France"]},{"name":"Institut Cochin, Universit\u00e9 Paris Descartes , Paris 75014,","place":["France"]},{"name":"Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 8104 , Paris 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Millet","sequence":"additional","affiliation":[{"name":"INSERM U1016 , Paris 75014,","place":["France"]},{"name":"Institut Cochin, Universit\u00e9 Paris Descartes , Paris 75014,","place":["France"]},{"name":"Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 8104 , Paris 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Pederzoli-Ribeil","sequence":"additional","affiliation":[{"name":"INSERM U1016 , Paris 75014,","place":["France"]},{"name":"Institut Cochin, Universit\u00e9 Paris Descartes , Paris 75014,","place":["France"]},{"name":"Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 8104 , Paris 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Tacnet-Delorme","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Joseph Fourier Grenoble 1, Institut de Biologie Structurale Jean-Pierre Ebel , Grenoble F-38027 Cedex 1,","place":["France"]},{"name":"Centre National de la Recherche Scientifique , Grenoble F-38000,","place":["France"]},{"name":"Commissariat \u00e0 l\u2019Energie Atomique, Institut de Biologie Structurale Jean-Pierre Ebel , Grenoble F-38000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Guillevin","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne, H\u00f4pital Cochin , Paris 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Mouthon","sequence":"additional","affiliation":[{"name":"INSERM U1016 , Paris 75014,","place":["France"]},{"name":"Institut Cochin, Universit\u00e9 Paris Descartes , Paris 75014,","place":["France"]},{"name":"Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 8104 , Paris 75014,","place":["France"]},{"name":"Service de M\u00e9decine Interne, H\u00f4pital Cochin , Paris 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Frachet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Joseph Fourier Grenoble 1, Institut de Biologie Structurale Jean-Pierre Ebel , Grenoble F-38027 Cedex 1,","place":["France"]},{"name":"Centre National de la Recherche Scientifique , Grenoble F-38000,","place":["France"]},{"name":"Commissariat \u00e0 l\u2019Energie Atomique, Institut de Biologie Structurale Jean-Pierre Ebel , Grenoble F-38000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Witko-Sarsat","sequence":"additional","affiliation":[{"name":"INSERM U1016 , Paris 75014,","place":["France"]},{"name":"Institut Cochin, Universit\u00e9 Paris Descartes , Paris 75014,","place":["France"]},{"name":"Centre National de la Recherche Scientifique-Unit\u00e9 Mixte de Recherche 8104 , Paris 75014,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,1]]},"reference":[{"key":"2025032409230541600_r1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.autrev.2011.08.002","article-title":"Immune regulatory mechanisms in ANCA-associated vasculitides","volume":"11","author":"Lepse","year":"2011","journal-title":"Autoimmun. 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