{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:50:55Z","timestamp":1791010255424,"version":"4.1.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract.<\/jats:title>\n                    <jats:p>Wegener's granulomatosis is an autoimmune disease that is characterized by systemic vasculitis and granuloma formation. Early influx of polymorphonuclear neutrophils (PMN), followed at a later stage by mononuclear cells, contributes to the granulomatous inflammation. Previous studies have shown that proteinase 3 (PR3), the major autoantigen in Wegener's granulomatosis, specifically binds to endothelial cells and plays a possible role in activation of these cells by enhancing interleukin-8 production, thus providing a chemotactic and activating stimulus for PMN. The present study demonstrated that PR3 enhances the production of monocyte chemoattractant protein-1 (MCP-1) by human umbilical vein endothelial cells (HUVEC) in a dose- and time-dependent manner. The PR3-induced increase in MCP-1 production was demonstrated at both the protein and the mRNA levels and was chemotactic for monocytes. In addition, it was demonstrated that PR3 induces a dose- and time-dependent increase in the expression of intercellular adhesion molecule-1 (ICAM-1) as determined by fluorescence-activated cell sorter analysis. The PR3-induced increase in expression of ICAM-1 was also demonstrated at the mRNA level. PR3 induced a slight increase in vascular cell adhesion molecule-1 expression and had no effect on the expression of both P- and E-selectin. Incubation of HUVEC for 24 h in the presence of PR3 resulted in a significant increase in adhesion of PMN, which was reduced to baseline levels in the presence of blocking monoclonal antibody anti\u2014ICAM-1 or anti-CD18 or a combination of both. Monocytes showed a slight but statistically not significant increase in adhesion. Incubation of HUVEC with PR3 for 4 h did not result in enhanced adhesion of either PMN or monocytes. It was hypothesized that PR3, which may be released locally at inflammatory sites after activation of cytokineprimed PMN, plays a role in endothelial cell activation by enhancing both interleukin-8 and MCP-1 production, thus providing a chemotactic and activating stimulus for both PMN and monocytes. In addition, PR3 may contribute to the ongoing inflammation by enhancing the adhesion of PMN to endothelial cells by upregulating ICAM-1 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.v125932","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T18:09:31Z","timestamp":1619460571000},"page":"932-940","source":"Crossref","is-referenced-by-count":69,"title":["Proteinase 3 Enhances Endothelial Monocyte Chemoattractant Protein-1 Production and Induces Increased Adhesion of Neutrophils to Endothelial Cells by Upregulating Intercellular Cell Adhesion Molecule-1"],"prefix":"10.1681","volume":"12","author":[{"given":"MIRIAM E. J.","family":"TAEKEMA-ROELVINK","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CEES","family":"VAN KOOTEN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SANDRA","family":"VAN DER KOOIJ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EVERT","family":"HEEMSKERK","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MOHAMED R.","family":"DAHA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-200105000-00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:25:46Z","timestamp":1786130746000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-200105000-00008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.v125932","relation":{},"ISSN":["1046-6673"],"issn-type":[{"value":"1046-6673","type":"print"}],"subject":[],"published":{"date-parts":[[2001,5]]}}}