{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:11:13Z","timestamp":1745554273045,"version":"3.40.4"},"reference-count":18,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2004,11,17]],"date-time":"2004-11-17T00:00:00Z","timestamp":1100649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2004,11,17]],"date-time":"2004-11-17T00:00:00Z","timestamp":1100649600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron Exp Nephrol"],"abstract":"<jats:p>&lt;i&gt;Background\/Aims:&lt;\/i&gt; Integrins are adhesion molecules of fundamental importance to the recruitment of leucocytes in inflammation. The \u03b14\u03b21 integrin (VLA-4) is a leucocyte ligand for endothelial vascular cell adhesion molecule-1 (VCAM-1), fibronectin and osteopontin. We addressed the role of VLA-4 in mediating progressive renal injury in vivo using a blocking monoclonal antibody (mAb) in a rat model of crescentic glomerulonephritis. &lt;i&gt;Methods:&lt;\/i&gt; WKY rats with nephrotoxic nephritis were given anti-VLA-4 or control mAb at 2.5 mg\/kg by i.p. injection on alternate days. In separate experiments, antibodies were given from days 5\u201313, from days 13\u201321 or from days 14\u201328. &lt;i&gt;Results:&lt;\/i&gt; Early treatment with anti-VLA-4 mAb from days 5\u201313 showed a significant effect on renal function, with a reduction in albuminuria (p &lt; 0.01) and a higher creatinine clearance (p &lt; 0.05). Delayed treatment from days 13\u201321 also showed a reduction in albuminuria (p &lt; 0.05) and serum creatinine (p &lt; 0.05). However, there was no significant effect on glomerular or interstitial scarring in these two experiments. In the late treatment study, in which anti-VLA-4 mAb was administered from days 14\u201328, serum creatinine was reduced (p &lt; 0.05), creatinine clearance was improved (p &lt; 0.05), and renal survival was significantly prolonged (p &lt; 0.05). Interstitial scarring was significantly less in treated rats (p &lt; 0.05). Glomerular macrophage and CD8+ cell counts were higher in anti-VLA-4 mAb treated rats (p &lt; 0.05), possibly reflecting greater glomerular scarring in control animals. &lt;i&gt;Conclusion:&lt;\/i&gt; Leucocyte VLA-4 mediates pro-inflammatory and pro-fibrotic effects within the kidney, independent of any role in recruitment of leucocytes into the kidney. Blocking VLA-4 is a promising therapeutic approach in human glomerulonephritis.<\/jats:p>","DOI":"10.1159\/000074326","type":"journal-article","created":{"date-parts":[[2003,12,19]],"date-time":"2003-12-19T09:25:47Z","timestamp":1071825947000},"page":"e100-e110","source":"Crossref","is-referenced-by-count":9,"title":["Blocking VLA-4 Prevents Progression of Experimental Crescentic Glomerulonephritis"],"prefix":"10.1159","volume":"95","author":[{"given":"Sarah B.","family":"Khan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gurjeet","family":"Bhangal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy R.","family":"Lobb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Terence","family":"Cook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles D.","family":"Pusey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2004,11,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90279-8"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90337-9"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.125.1.215"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.124.4.601"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.128.6.1243"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1021\/jm980673g"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.19.1.20.5340"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1080\/000164800750000315"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00491-3"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2175"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.148.1.246"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00354.x"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.125.5.1165"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.5002"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4941"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00083.x"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201100200"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.3.873"}],"container-title":["Nephron Experimental Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/74326","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/74326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:52:18Z","timestamp":1745466738000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000074326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,11,17]]},"references-count":18,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2003,11,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000074326","archive":["Portico"],"relation":{},"ISSN":["1660-2129"],"issn-type":[{"type":"electronic","value":"1660-2129"}],"subject":[],"published":{"date-parts":[[2004,11,17]]}}}