Soluble TNF binding proteins modulate the negative inotropic properties of TNF-α in vitro Academic Article uri icon

Overview

MeSH Major

  • Carrier Proteins
  • Myocardial Contraction
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha

abstract

  • Soluble tumor necrosis factor (TNF) binding proteins (TNF-BPs) were characterized with respect to their capacity to modulate the negative inotropic properties of TNF-alpha in isolated contracting cardiac myocytes. Three TNF-BPs were evaluated: two natural monomeric human TNF monomeric binding proteins, TNF-BP1 and TNF-BP2, and sTNFR:Fc, a dimer of two molecules of human TNF-BP2 linked by the Fc portion of the human immunoglobulin G1 molecule. When TNF-alpha (25 pM) was allowed to form TNF-BP-TNF-alpha complexes, the negative inotropic effects of TNF-alpha were completely prevented by "neutralizing concentrations" of TNF-BPs, whereas lesser concentrations of TNF-BPs only partially attenuated the negative inotropic effects of TNF-alpha. The dimeric binding protein sTNFR:Fc was more effective on a molar basis than either of the monomeric binding proteins (TNF-BP1 or TNF-BP2) with respect to blocking the negative inotropic effects of TNF-alpha. When cardiac myocytes that had been treated with TNF-alpha (25 pM) were exposed to neutralizing concentrations of TNF-BP1, TNF-BP2, and sTNFR:Fc, the negative inotropic effects were completely reversed within 30 min. Thus these studies show for the first time that TNF-BPs are sufficient to prevent, as well as reverse, the negative inotropic properties of TNF-alpha in vitro.

publication date

  • January 1995

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 7864177

Additional Document Info

start page

  • H517

end page

  • 25

volume

  • 268

number

  • 2 37-2