The lectin-like domain of tumor necrosis factor-α increases membrane conductance in microvascular endothelial cells and peritoneal macrophages

Marusa Hribar, Alain Bloc, F. Gisou Van Der Goot, Lucie Fransen, Patrick De Baetselier, Georges E. Grau, Horst Bluethmann, Michael A. Matthay, Yves Dunant, Jérôme Pugin, Rudolf Lucas

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Herein, we show that TNF exerts a pH-dependent increase in membrane conductance in primary lung microvascular endothelial cells and peritoneal macrophages. This effect was TNF receptor-independent, since it also occurred in cells isolated from mice deficient in both types of TNF receptors. A TNF mutant in which the three amino acids critical for the lectin-like activity were replaced by an alanine did not show any significant effect on membrane conductance. Moreover, a synthetic 17-amino acid peptide of TNF, which was previously shown to exert lectin-like activity, also increased the ion permeability in these cells. The amiloride sensitivity of the observed activity suggests a binding of TNF to an endogenous ion channel rather than channel formation by TNF itself. This may have important implications in mechanisms of TNF-mediated vascular pathology.

Original languageEnglish (US)
Pages (from-to)3105-3111
Number of pages7
JournalEuropean Journal of Immunology
Volume29
Issue number10
DOIs
Publication statusPublished - Oct 26 1999
Externally publishedYes

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Keywords

  • Conductance
  • Endothelium
  • TNF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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