| Title: |
Inhibition of lipopolysaccharide and IL-1 but not of TNF-induced activation of human endothelial cells by suramin. |
| Authors: |
Strassmann, G; Graber, N; Goyert, S M; Fong, M; McCullers, S; Rong, G W; Beall, L D |
| Source: |
The Journal of Immunology ; volume 153, issue 5, page 2239-2247 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
1994 |
| Description: |
The binding and trans-endothelium migration of inflammatory cells is believed to play a critical role in a variety of inflammatory conditions. This study investigates the ability of the experimental drug suramin to block the activation of HUVEC by endotoxin and by the proinflammatory cytokines IL-1 and TNF. We demonstrate that the inducible expression of several adhesion molecules by LPS and IL-1 beta but not by TNF-alpha is prevented by suramin. In a dose-dependent manner, suramin inhibits the binding of neutrophils and T lymphocytes to LPS and IL-1 beta but not to TNF-alpha-activated HUVEC. The inhibitory effect of the drug on IL-1 beta-induced but not on LPS-induced cell stimulation can be completely reversed by the addition of excess cytokine but not by excess LPS. Because LPS activation of HUVEC is known to depend on serum/plasma-derived soluble CD14, we set out to determine whether suramin inhibition involves interference with the action of the CD14-LPS complex on HUVEC. Indeed, the drug prevents the binding of radioactive LPS in the presence of serum and inhibits LPS-induced cell activation in serum-free medium supplemented with recombinant soluble CD14. The results suggest that suramin interferes with the CD14-dependent activation of HUVEC and that it also may be a useful agent in blocking infectious endotheliopathies in vivo. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.153.5.2239 |
| Availability: |
https://doi.org/10.4049/jimmunol.153.5.2239; https://academic.oup.com/jimmunol/article-pdf/153/5/2239/62396462/2239.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.D3F49568 |
| Database: |
BASE |