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 conduct ance in primary lung microvascular endothelial cells and peritoneal macroph ages. This effect was TNF receptor-independent, since it also occurred in c ells isolated from mice deficient in both types of TNF receptors. A TNF mut ant in which the three amino acids critical for the lectinlike activity wer e replaced by an alanine did not show any significant effect on membrane co nductance. Moreover, a synthetic 17-amino acid peptide of TNF, which was pr eviously shown to exert lectin-like activity, also increased the ion permea bility in these cells. The amiloride sensitivity of the observed activity s uggests a binding of TNF to an endogenous ion channel rather than channel f ormation by TNF itself. This may have important implications in mechanisms of TNF-mediated vascular pathology.