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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-10-10
pubmed:abstractText
The initial event in the process of leukocyte infiltration is characterized by leukocyte rolling on the surface of the endothelium, which is mediated by selectins. P- and L-selectin bind to the sulphated sugar chains of their natural ligands, including sulphated glycolipids such as sulphatide. Recently, it has been demonstrated that sulphated glycolipids and sulphated oligosaccharides interfere with selectin binding pathways. This study synthesized sulphated hyaluronic acid (SHA), which is a potential selectin-blocking agent, and examined its therapeutic effect on the experimental progressive mesangial proliferative glomerulonephritis induced by anti-Thy-1 monoclonal antibody (1-22-3 MAb) after unilateral nephrectomy. The selectin-inhibitory effect of SHA in vitro was confirmed. SHA inhibited the binding of P- and L-selectin to sulphatide, which is a glycolipid ligand for P- and L-selectin, at a concentration of 1.5 micro g/ml and 100 micro g/ml. Immunohistochemical examination showed that P-selectin was up-regulated in the glomeruli in the 1-22-3 MAb nephritis model, while the ligands for L-selectin were not detected in the glomerular tufts. A single administration of SHA ameliorated proteinuria and glomerular leukocyte infiltration in 24 h after the injection of anti-Thy-1 MAb. Anti-P-selectin MAb, but not anti-L-selectin MAb, inhibited proteinuria and glomerular leukocyte infiltration. To examine further the therapeutic effect of SHA on chronic glomerulonephritis, SHA was administered daily from day 3 to day 14 in this model. Proteinuria and glomerular leukocyte infiltration were significantly diminished in SHA-treated rats on day 14. These results suggest that SHA ameliorated rat progressive mesangial proliferative glomerulonephritis by inhibiting P-selectin-dependent leukocyte infiltration in glomeruli. Sulphated oligosaccharides may be beneficial for the therapy of mesangial proliferative glomerulonephritis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright 2002 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
198
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
407-14
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12375274-Animals, pubmed-meshheading:12375274-Antibodies, Monoclonal, pubmed-meshheading:12375274-Chemotaxis, Leukocyte, pubmed-meshheading:12375274-Disease Progression, pubmed-meshheading:12375274-Dose-Response Relationship, Drug, pubmed-meshheading:12375274-Female, pubmed-meshheading:12375274-Glomerulonephritis, Membranoproliferative, pubmed-meshheading:12375274-Hyaluronic Acid, pubmed-meshheading:12375274-Kidney Glomerulus, pubmed-meshheading:12375274-L-Selectin, pubmed-meshheading:12375274-Leukocyte Count, pubmed-meshheading:12375274-P-Selectin, pubmed-meshheading:12375274-Proteinuria, pubmed-meshheading:12375274-Rats, pubmed-meshheading:12375274-Rats, Wistar, pubmed-meshheading:12375274-Selectins, pubmed-meshheading:12375274-Sulfates, pubmed-meshheading:12375274-Sulfoglycosphingolipids
pubmed:year
2002
pubmed:articleTitle
Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis.
pubmed:affiliation
Department of Medicine III, Okayama University Medical School, Japan. mm8059@kchnet.or.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't