Effects of a new synthetic selectin blocker in an acute rat thrombotic glomerulonephritis

Isao Ito, Yukio Yuzawa, Masashi Mizuno, Kazuhiro Nishikawa, Akira Tashita, Takahito Jomori, Nigishi Hotta, Seiichi Matsuo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In an attempt to explore a novel therapeutic approach, a new synthetic sulfatide derivative (SKK60037) was evaluated in an acute rat model of P-selectin and leukocyte-dependent thrombotic glomerulonephritis (TG). In vitro, SKK60037 inhibits the function of P- and L-selectin more effectively than sialyl Lewis X (sLex), a well-established selectin blocker. TG was induced by the intravenous administration of nephrotoxic globulin (NTG) to rats pretreated with a subclinical dose of lipopolysaccharide. In this model, platelet accumulation was remarkable within 10 minutes after induction of disease, followed by the infiltration of leukocytes, mainly neutrophils and macrophages. Thrombus formation and fibrinogen deposition in the glomeruli were observed within 1 hour, and they proceeded until 6 hours. P-selectin was highly expressed in glomeruli, whereas E-selectin and L-selectin ligands were not detected. We tested the effects of SKK60037 in this model in comparison with sLex and antirat P-selectin monoclonal antibody (ARP2-4). SKK60037 blocked platelet accumulation in glomerular capillaries at 10 minutes after NTG injection. At 6 hours, leukocyte infiltration and thrombosis were significantly suppressed. Protective effects of SKK60037 were similar to those of ARP2-4, whereas sLex showed minimum effect. The superior effects and more favorable characteristics of SKK60037 to sLex suggest the potential of SKK60037 for clinical application.

Original languageEnglish
Pages (from-to)265-273
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume38
Issue number2
DOIs
Publication statusPublished - 01-01-2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Nephrology

Fingerprint Dive into the research topics of 'Effects of a new synthetic selectin blocker in an acute rat thrombotic glomerulonephritis'. Together they form a unique fingerprint.

  • Cite this