Inhibition of adhesion of human neutrophils and eosinophils to P-selectin by the sialyl Lewis antagonist TBC1269: preferential activity against neutrophil adhesion in vitro

J Allergy Clin Immunol. 2000 Apr;105(4):769-75. doi: 10.1067/mai.2000.105121.


Background: Leukocyte rolling on vascular endothelium is mediated by selectins and their carbohydrate-containing counterligands. The tetrasaccharide sialyl Lewis(x) (sLe(x)) binds to all 3 selectins, so compounds that mimic sLe(x) are potential antagonists.

Objective: Our purpose was to examine the ability of the sLe(x) mimetic TBC1269 to inhibit binding of human neutrophils and eosinophils to P-selectin.

Methods: Expression of the primary P-selectin ligand, P-selectin glycoprotein ligand-1 (PSGL-1), was examined on neutrophils and eosinophils, and their adhesion to immobilized P-selectin was examined under both static and dynamic conditions in the presence and absence of TBC1269.

Results: Neutrophils and eosinophils expressed PSGL-1, with eosinophils expressing about twice as much as neutrophils. In the absence of TBC1269, both cell types adhered avidly to P-selectin under static and dynamic conditions. For neutrophils, preincubation of P-selectin-coated plates with TBC1269 (1 to 1000 microgram/mL) resulted in concentration-dependent decreases in neutrophil adhesion, with significant inhibition seen at concentrations >/=100 microgram/mL. Eosinophil adhesion to P-selectin was more refractory to inhibition by TBC1269 and was only partially inhibited at the highest concentration tested (1000 microgram/mL). Two structurally related control compounds, TBC1900 and TBC746, had no effect when tested at similar concentrations.

Conclusion: These data indicate that an sLe(x) mimetic can exhibit cell type-specific differences in potencies with respect to antagonism of P-selectin adhesion. Although this may in part be the result of differences in PSGL-1 expression, the discrepancy in potencies may also be due to other differences, including carbohydrate composition and binding affinity of PSGL-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Asthmatic Agents / pharmacology*
  • Biphenyl Compounds / pharmacology*
  • Cell Adhesion / drug effects
  • Eosinophils / cytology*
  • Humans
  • Lewis Blood Group Antigens
  • Mannose / analogs & derivatives
  • Mannosides / pharmacology*
  • Neutrophils / cytology*
  • Oligosaccharides / antagonists & inhibitors*
  • P-Selectin / drug effects
  • P-Selectin / pharmacology*
  • Sialyl Lewis X Antigen


  • Anti-Asthmatic Agents
  • Biphenyl Compounds
  • Lewis Blood Group Antigens
  • Mannosides
  • Oligosaccharides
  • P-Selectin
  • Sialyl Lewis X Antigen
  • bimosiamose disodium
  • Mannose