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.
Hribar
M
M
Division of Medical Intensive Care, Department of Internal Medicine, University of Geneva, Geneva, Switzerland.
Bloc
A
A
van der Goot
F G
FG
Fransen
L
L
De Baetselier
P
P
Grau
G E
GE
Bluethmann
H
H
Matthay
M A
MA
Dunant
Y
Y
Pugin
J
J
Lucas
R
R
D000818:Animals; D002199:Capillary Permeability / Q000276:immunology; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D037102:Lectins / Q000276:immunology / Q000502:physiology*; D008168:Lung / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D008833:Microcirculation / Q000166:cytology / Q000276:immunology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D037102:Lectins; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha