Preventive effect of sulphated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally induced crescentic glomerulonephritis
Authors: OGAWA, D.1; SHIKATA, K.1; MATSUDA, M.1; OKADA, S.1; WADA, J.1; YAMAGUCHI, S.2; SUZUKI, Y.3; MIYASAKA, M.4; TOJO, S.5; MAKINO, H.1
Source: Clinical & Experimental Immunology, Volume 129, Number 1, July 2002 , pp. 43-53(11)
Publisher: Blackwell Publishing
- Free Content
- New Content
- Subscribed Content
- Free Trial Content
Abstract:
SUMMARY Leucocytes infiltrate into renal tissue and are involved in the pathogenesis of crescentic glomerulonephritis. The initial event in the process of leucocyte infiltration is characterized by selectin-mediated leucocyte rolling on endothelial surface. Role of selectins in pathogenesis of glomerulonephritis has still been controversial. Sulphated glycolipids and sulphated polysaccharides interfere with the binding of P- and L-selectin with carbohydrate ligands on endothelial cells or on leucocytes. Here we evaluated the role of selectins and the preventive effects of sulphated colominic acid (SCA), a synthetic sulphated polysaccharide, on experimental crescentic glomerulonephritis in Wistar-Kyoto (WKY) rats. Crescentic glomerulonephritis was induced by injection of nephrotoxic serum (NTS) in WKY rats. Rats subsequently received intraperitoneal injection of saline, neutralizing or non-neutralizing monoclonal antibody (mAb) to rat P-selectin and L-selectin, SCA (5 or 10mg/kg/day) or nonsulphated colominic acid (CA) (10mg/kg/day) for 2 weeks. Localization of P-, E-selectin, ligands for L-selectin and intraglomerular leucocytes was examined by immunohistochemistry. Gene expression of platelet-derived growth factor (PDGF) B chain in glomeruli was quantified using real-time RT-PCR. P-selectin was highly expressed on glomerular endothelial cells after injection of NTS, whereas E-selectin and L-selectin ligands were not detected. Anti-P-selectin mAb, but not anti-L-selectin mAb, significantly reduced glomerular infiltration of macrophages, crescent formation, and proteinuria. SCA also reduced proteinuria, macrophage infiltration, and crescent formation in a dose-dependent manner. Furthermore, SCA suppressed gene expression of PDGF B chain in glomeruli. Our results indicate that P-selectin partially mediate glomerular infiltration of macrophage in experimental crescentic glomerulonephritis. Moreover, SCA may inhibit intraglomerular infiltration of macrophages by interfering with P-selectin-dependent adhesion pathway, and progression of experimental crescentic glomerulonephritis.Keywords: selectin crescentic glomerulonephritis sulphated colominic acid platelet-derived growth factor
Document Type: Research article
DOI: 10.1046/j.1365-2249.2002.01875.x
Affiliations: 1: Department of Medicine III, Okayama University Medical School, Okayama, 2: Kyoto Research Laboratories, Marukin Chuyu Co. Ltd, Kyoto, 3: Department of Biochemistry, University of Shizuoka School of Pharmaceutical Science, Shizuoka, 4: Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, Osaka and 5: Research Center, Sumitomo Pharmaceuticals Co. Ltd, Osaka, Japan
- Free Content
- New Content
- Subscribed Content
- Free Trial Content
Click here for Page Help