The lectin-like domain of tumor necrosis factor-alpha increases membrane conductance in microvascular endothelial cells and peritoneal macrophages
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.
Keywords: Animals ; Capillary Permeability/immunology ; Electric Conductivity ; Endothelium ; Vascular/cytology/immunology/*physiology ; Lectins/immunology/*physiology ; Lung/*blood supply/immunology/metabolism ; Macrophages ; Peritoneal/immunology/*physiology ; Male ; Membrane Potentials/immunology ; Mice ; Mice ; Inbred C57BL ; Mice ; Inbred CBA ; Mice ; Mutant Strains ; Microcirculation/cytology/immunology ; Patch-Clamp Techniques ; Peptide Fragments/immunology/*physiology ; Tumor Necrosis Factor-alpha/*physiology
Division of Medical Intensive Care, Department of Internal Medicine, University of Geneva, Geneva, Switzerland.
Record created on 2009-01-30, modified on 2016-08-08