Dichotomal role of TNF in experimental pulmonary edema reabsorption

Clemens Braun, Jürg Hamacher, Denis R. Morel, Albrecht Wendel, Rudolf Lucas

Research output: Contribution to journalArticle

52 Citations (Scopus)

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′-diacetylcnitobiose. 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 cotreatment 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.

Original languageEnglish (US)
Pages (from-to)3402-3408
Number of pages7
JournalJournal of Immunology
Volume175
Issue number5
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Fingerprint

Pulmonary Edema
Lectins
Binding Sites
Oligosaccharides
Lung
Edema
Cytokines
Peptides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dichotomal role of TNF in experimental pulmonary edema reabsorption. / Braun, Clemens; Hamacher, Jürg; Morel, Denis R.; Wendel, Albrecht; Lucas, Rudolf.

In: Journal of Immunology, Vol. 175, No. 5, 01.09.2005, p. 3402-3408.

Research output: Contribution to journalArticle

Braun, Clemens ; Hamacher, Jürg ; Morel, Denis R. ; Wendel, Albrecht ; Lucas, Rudolf. / Dichotomal role of TNF in experimental pulmonary edema reabsorption. In: Journal of Immunology. 2005 ; Vol. 175, No. 5. pp. 3402-3408.
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