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We hypothesized that such MEC characteristics might shape their interaction with NK cells through the use of different adhesion molecules and NK cell receptor ligands or the release of different soluble factors and render them more or less vulnerable to NK cell injury during autoimmune vasculitis, such as granulomatosis with polyangiitis (GPA). To generate a comprehensive expression profile of human MECs of renal, lung, and dermal tissue origin, we characterized, in detail, their response to inflammatory cytokines and to proteinase 3, a major autoantigen in GPA, and analyzed the effects on NK cell activation. In this study, we show that renal MECs were more susceptible than lung and dermal MECs to the effect of inflammatory signals, showing upregulation of ICAM-1 and VCAM-1 on their surface, as well as release of CCL2, soluble fractalkine, and soluble VCAM-1. Proteinase 3\u2013stimulated renal and lung MECs triggered CD107a degranulation in control NK cell. Notably, NK cells from GPA patients expressed markers of recent in vivo activation (CD69, CD107a), degranulated more efficiently than did control NK cells in the presence of renal MECs, and induced direct killing of renal MECs in vitro. These results suggest that, upon inflammatory conditions in GPA, renal MECs may contribute to the recruitment and activation of NK cells in the target vessel wall, which may participate in the necrotizing vasculitis of the kidney during this disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1301508","type":"journal-article","created":{"date-parts":[[2014,3,6]],"date-time":"2014-03-06T04:02:09Z","timestamp":1394078529000},"page":"3399-3408","source":"Crossref","is-referenced-by-count":24,"title":["Tissue-Specific Microvascular Endothelial Cells Show Distinct Capacity To Activate NK Cells: Implications for the Pathophysiology of Granulomatosis with Polyangiitis"],"prefix":"10.1093","volume":"192","author":[{"given":"Sara","family":"Tognarelli","sequence":"first","affiliation":[{"name":"INSERM, U1016 H\u00f4pital Saint-Vincent de Paul , 75014 Paris,","place":["France"]},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes , 75014 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Gayet","sequence":"additional","affiliation":[{"name":"INSERM, U1016 H\u00f4pital Saint-Vincent de Paul , 75014 Paris,","place":["France"]},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes , 75014 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Lambert","sequence":"additional","affiliation":[{"name":"INSERM, U1016 H\u00f4pital Saint-Vincent de Paul , 75014 Paris,","place":["France"]},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes , 75014 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Dupuy","sequence":"additional","affiliation":[{"name":"INSERM, U1016 H\u00f4pital Saint-Vincent de Paul , 75014 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Karras","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes , 75014 Paris,","place":["France"]},{"name":"Service de N\u00e9phrologie, Assistance Publique \u2013 H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou , 75015 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Cohen","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes , 75014 Paris,","place":["France"]},{"name":"Service de M\u00e9decine Interne, Assistance Publique \u2013 H\u00f4pitaux de Paris, H\u00f4pital Cochin , 75014 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Guillevin","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Descartes , 75014 Paris,","place":["France"]},{"name":"Service de M\u00e9decine Interne, Assistance Publique \u2013 H\u00f4pitaux de Paris, H\u00f4pital Cochin , 75014 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"de Menthon","sequence":"additional","affiliation":[{"name":"INSERM, U1016 H\u00f4pital Saint-Vincent de Paul , 75014 Paris,","place":["France"]},{"name":"Service de M\u00e9decine Interne, Assistance Publique \u2013 H\u00f4pitaux de Paris, H\u00f4pital Saint-Louis , 75010 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Caillat-Zucman","sequence":"additional","affiliation":[{"name":"INSERM, U1016 H\u00f4pital Saint-Vincent de Paul , 75014 Paris,","place":["France"]},{"name":"Laboratoire d\u2019Immunologie, Assistance Publique \u2013 H\u00f4pitaux de Paris, H\u00f4pital Robert Debr\u00e9 , 75019 Paris,","place":["France"]},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Diderot , 75013 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,1]]},"reference":[{"key":"2025032404212029500_r1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1152\/physrev.1990.70.2.427","article-title":"Cytokines and endothelial cell biology","volume":"70","author":"Pober","year":"1990","journal-title":"Physiol. 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