Inhibition of P-selectin specific cell adhesion by a low molecular weight, non-carbohydrate compound, KF38789.

Abstract

OBJECTIVE AND DESIGN:

P-selectin is a cell adhesion molecule of the selectin family. This study evaluated the effects of novel, low molecular weight P-selectin inhibitors in a cell adhesion assay and a murine model of peritonitis.

MATERIALS:

U937 or HL60 was used for cell adhesion assay. Human polymorphonuclear cells were studied for the production of superoxide. BALB/c mice were used for the in vivo study.

TREATMENT:

The thioglycollate (TG)-induced accumulation of leukocytes in mice was measured 6 h after the treatment. KF38789 or antibody (1 mg/kg) was injected intravenously prior to TG injection and at 3 h following initial injection.

RESULTS:

Low molecular weight, non-carbohydrate inhibitors against P-selectin- mediated cell adhesion were tested. One of the most potent inhibitors, KF38789, inhibited the binding of U937 cells to immobilized P-selectin immunoglobulin G chimeric protein (P-selectin-Ig) with an IC50 value of 1.97 microM. Cell adhesion to both E-selectin-Ig and L-selectin-Ig were not affected even by 100 microM of KF38789. Moreover, KF38789 inhibited P-selectin-induced superoxide production from human polymorphonuclear cells. Intravenously injected KF38789 significantly inhibited the TG-induced accumulation of leukocytes in the mouse peritoneal cavity (p<0.01).

CONCLUSION:

A novel low molecular weight compound, KF38789, specifically inhibited P-selectin-dependent cell adhesion and the leukocyte recruitment in mouse peritonitis.

• Authors: S Ohta, Y Inujima, M Abe, Y Uosaki, S Sato, I Miki
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 50 Issue 11 Pg. 544-51 (Nov 2001) ISSN: 1023-3830 [Print] Switzerland
• PMID: 11766994 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• KF38789
• Oligosaccharides
• P-Selectin
• Pyrones
• Sialyl Lewis X Antigen
• Thioglycolates
• Superoxides

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Cell Adhesion (drug effects)
• Humans
• Mice
• Mice, Inbred BALB C
• Neutrophils (drug effects, physiology)
• Oligosaccharides (metabolism)
• P-Selectin (drug effects, physiology)
• Peritonitis (prevention & control)
• Pyrones (pharmacology)
• Sialyl Lewis X Antigen
• Superoxides (metabolism)
• Thioglycolates (toxicity)
• U937 Cells