{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:03:44Z","timestamp":1768345424562,"version":"3.49.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Among the anti-neutrophil cytoplasmic Abs (ANCA), those targeting proteinase 3 (PR3) have a high sensitivity and specificity for Wegener\u2019s granulomatosis (WG). A pathogenetic role for these autoantibodies has been proposed due to their capacity of activating neutrophils in vitro. Recently, PR3 was also detected in human renal tubular epithelial cells (TEC). In the present study, the effect of murine monoclonal anti-PR3 Abs (anti-PR3) and purified c-ANCA targeting PR3 from WG serum on isolated human renal tubular cell signaling and inflammatory mediator release was characterized. Priming of TEC with TNF-\u03b1 resulted in surface expression of PR3, as quantified in immunofluorescence studies and by flow cytometry. Moreover, PR3 was immunoprecipitated on surface-labeled TEC. Primed TEC responded to anti-PR3 with a dose- and time-dependent activation of phosphoinositide hydrolysis, resulting in a remarkable accumulation of inositolphosphates. Control IgG was entirely ineffective, whereas PR3-ANCA reproduced the phosphoinositide response. The signaling response was accompanied by a pronounced release of superoxidanion into the cell supernatant. Moreover, large amounts of PGE2 and, to a lesser extent, of thromboxane B2, the stable metabolite of TxA2, were secreted from anti-PR3-stimulated TEC. In parallel, a rise in intracellular cAMP levels was observed, which was blocked by the cyclooxygenase inhibitor indomethacin. We conclude that anti-PR3 Abs directly target renal TECs, thereby provoking pronounced activation of the phosphoinositide-related signal transduction pathway. Associated metabolic events such as the release of reactive oxygen species and lipid mediators may directly contribute to the development of renal lesions and loss of kidney function in WG.<\/jats:p>","DOI":"10.4049\/jimmunol.168.6.3057","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T00:31:13Z","timestamp":1398040273000},"page":"3057-3064","source":"Crossref","is-referenced-by-count":7,"title":["Interaction of Antibodies to Proteinase 3 (Classic Anti-Neutrophil Cytoplasmic Antibody) with Human Renal Tubular Epithelial Cells: Impact on Signaling Events and Inflammatory Mediator Generation"],"prefix":"10.1093","volume":"168","author":[{"given":"Katja","family":"Hattar","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Grandel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"Bickenbach","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Schwarting","sequence":"additional","affiliation":[{"name":"First Medical Department, University of Mainz , Mainz ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner-Johannes","family":"Mayet","sequence":"additional","affiliation":[{"name":"First Medical Department, University of Mainz , Mainz ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju\u0308rgen","family":"Bux","sequence":"additional","affiliation":[{"name":"Institute for Clinical Immunology and Transfusion Medicine, Department of Urology, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So\u0308nke","family":"Jessen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Urology, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrich","family":"Grimminger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf","family":"Sibelius","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University , Giessen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,3,15]]},"reference":[{"key":"2025032712351133700_R1","first-page":"285","volume-title":"Lupus","year":"1998"},{"key":"2025032712351133700_R2","first-page":"76","volume-title":"Ann. 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