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

Citation
S. Ohta et al., Inhibition of P-selectin specific cell adhesion by a low molecular weight,non-carbohydrate compound, KF38789, INFLAMM RES, 50(11), 2001, pp. 544-551
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INFLAMMATION RESEARCH
ISSN journal
1023-3830 → ACNP
Volume
50
Issue
11
Year of publication
2001
Pages
544 - 551
Database
ISI
SICI code
1023-3830(200111)50:11<544:IOPSCA>2.0.ZU;2-0
Abstract
Objective and design: P-selectin is a cell adhesion molecule of the selecti n family. This study evaluated the effects of novel, low molecular weight P -selectin inhibitors in a cell adhesion assay and a murine model of periton itis. Materials: U937 or 14L60 was used for cell adhesion assay. Human polymorpho nuclear cells were studied for the production of superoxide. BALB/c mice we re used for the in vivo study. Treatment: The thioglycollate (TG)-induced accumulation of leukocytes in mi ce 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 i njection. Results: Low molecular weight, non-carbohydrate inhibitors against P-select in- mediated cell adhesion were tested. One of the most potent inhibitors, KF38789, inhibited the binding of U937 cells to immobilized P-selectin immu noglobulin G chimeric protein (P-selectin-Ig) with an IC50 value of 1.97 mu M. Cell adhesion to both E-selectin-Ig and L-selectin-Ig were not affected even by 100 muM of KF38789. Moreover, Y,F38789 inhibited P-selectin-induced superoxide production from human polymorphonuclear cells. Intravenously in jected KF38789 significantly inhibited the TG-induced accumulation of leuko cytes in the mouse peritoneal cavity (p < 0.01). Conclusion: A novel low molecular weight compound, KF38789, specifically in hibited P-selectin-dependent cell adhesion and the leukocyte recruitment in mouse peritonitis.