Effect of Ebselen on polymorphonuclear leukocyte adhesion to and migration through cytokine-activated vascular endothelium

Andrew C. Issekutz, Nancy Lopes

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19 Citations (Scopus)

Abstract

Ebselen (PZ51, 2-Phenyl-1, 2-Benzoisoselenazol-3-(2H)-one) is a selinyl organic compound with anti-inflammatory properties. Some of its pharmacological effects are thought to result from its peroxidase activity. Here we examined the effects of Ebselen on polymorphonuclear leukocyte (PMNL) adhesion to umbilical vein endothelium and transendothelial migration in a modified Boyden chamber in which both PMNL-dependent and endothelial-dependent (IL-1, TNFα) PMNL adhesion and migration can be measured. Ebselen was found to dose dependently inhibit the adhesion of PMNL to IL-1 activated endothelium and to inhibit transendothelial PMNL migration induced by IL-1α, and TNFα with an ic50 value of 28 μM. Transendothelial migration induced by the PMNL chemotactic agents C5adesArg and N-formyl-norleu-leu-phe was also inhibited at slightly higher concentrations. The effect of Ebselen was not on endothelial cell activation but on PMNL activation for adhesion and migration. This effect on PMNL was irreversible for the duration of the assay period (75 min). The results that the anti-inflammatory activity of Ebselen may, in part, be due to direct inhibition of PMNL adhesion to vascular endothelium and transendothelial migration in response to a variety of inflammatory mediators.

Original languageEnglish
Pages (from-to)1383-1390
Number of pages8
JournalInternational Journal of Immunopharmacology
Volume14
Issue number8
DOIs
Publication statusPublished - Nov 1992

Bibliographical note

Funding Information:
Acknowledgements -- The authors are grateful to Ms L. Dunlop for excellent technical assistance, Mr K. MacLeod for preparation of figures, and Ms C. Fern for her expert secretarial help. The gifts of IL-la (Immunex, Corp.), TNFa (Genentech Inc.) and Ebselen (Natterman Res. Labs) are much appreciated and acknowledged in the Experimental Procedures. This work was supported in part by a Grant from CIBA-Geigy Pharmaceuticals and by Grant MA-7684 from the Medical Research Council of Canada.

ASJC Scopus Subject Areas

  • Immunology
  • Pharmacology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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Issekutz, A. C., & Lopes, N. (1992). Effect of Ebselen on polymorphonuclear leukocyte adhesion to and migration through cytokine-activated vascular endothelium. International Journal of Immunopharmacology, 14(8), 1383-1390. https://doi.org/10.1016/0192-0561(92)90009-A