title: Dichotomal role of TNF in experimental pulmonary edema reabsorption.
abstract: Distinct from its receptor binding sites, TNF carries a lectin-like domain, situated at the tip of the molecule, which specifically binds oligosaccharides, such as N,N'-diacetylchitobiose. In view of the apparently conflicting data concerning TNF actions in pulmonary edema, we investigated the contribution of, on the one hand, the receptor binding sites and, in contrast, the lectin-like domain of the cytokine on pulmonary fluid reabsorption in in situ and in vivo flooded rat lungs. Receptor binding sites were blocked with the human soluble TNFR type 1 construct (sTNFR1), whereas the lectin-like domain was blunted with the oligosaccharide N,N'-diacetylchitobiose. We observed that in situ, TNF failed to stimulate alveolar liquid clearance, but did so together with the sTNFR1, and this activity was neutralized by N,N'-diacetylchitobiose. In vivo TNF inhibited liquid clearance, but activated it when complexed with the sTNFR1. A TNF-derived peptide mimic of the lectin-like domain activated fluid reabsorption in flooded lungs, and this activity was blunted by co-treatment with TNF. Our results thus indicate that in these models the receptor binding sites of TNF inhibit, whereas its lectin-like domain activates, edema reabsorption.
authors.affiliation: Department of Biochemical Pharmacology, University of Konstanz, Konstanz, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Braun
authors.forename: Jürg
authors.initials: J
authors.lastname: Hamacher
authors.forename: Denis R
authors.initials: DR
authors.lastname: Morel
authors.forename: Albrecht
authors.initials: A
authors.lastname: Wendel
authors.forename: Rudolf
authors.initials: R
authors.lastname: Lucas
mesh_terms: D000042:Absorption; D000818:Animals; D001665:Binding Sites; D005260:Female; D037102:Lectins / Q000502:physiology*; D011654:Pulmonary Edema / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D037102:Lectins; D047888:Receptors, Tumor Necrosis Factor, Type I; D015222:Sodium Channels; D014409:Tumor Necrosis Factor-alpha