Hribar, M.Bloc, A.van der Goot, F. G.Fransen, L.De Baetselier, P.Grau, G. E.Bluethmann, H.Matthay, M. A.Dunant, Y.Pugin, J.Lucas, R.2009-01-302009-01-302009-01-30199910.1002/(SICI)1521-4141(199910)29:10<3105::AID-IMMU3105>3.0.CO;2-Ahttps://infoscience.epfl.ch/handle/20.500.14299/34613Herein, 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.AnimalsCapillary Permeability/immunologyElectric ConductivityEndotheliumVascular/cytology/immunology/*physiologyLectins/immunology/*physiologyLung/*blood supply/immunology/metabolismMacrophagesPeritoneal/immunology/*physiologyMaleMembrane Potentials/immunologyMiceMiceInbred C57BLMiceInbred CBAMiceMutant StrainsMicrocirculation/cytology/immunologyPatch-Clamp TechniquesPeptide Fragments/immunology/*physiologyTumor Necrosis Factor-alpha/*physiologytext::journal::journal article::research article