TY - JOUR
T1 - Soluble TNF binding proteins modulate the negative inotropic properties of TNF-α in vitro
AU - Kapadia, S.
AU - Torre-Amione, G.
AU - Yokoyama, T.
AU - Mann, D. L.
PY - 1995
Y1 - 1995
N2 - Soluble tumor necrosis factor (TNF) binding proteins (TNF-BPs) were characterized with respect to their capacity to modulate the negative inotropic properties of TNF-α 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-α (25 pM) was allowed to form TNF-BP-TNF-α complexes, the negative inotropic effects of TNF-α were completely prevented by 'neutralizing concentrations' of TNF-BPs, whereas lesser concentrations of TNF-BPs only partially attenuated the negative inotropic effects of TNF-α. 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-α. When cardiac myocytes that had been treated with TNF-α (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-α in vitro.
AB - Soluble tumor necrosis factor (TNF) binding proteins (TNF-BPs) were characterized with respect to their capacity to modulate the negative inotropic properties of TNF-α 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-α (25 pM) was allowed to form TNF-BP-TNF-α complexes, the negative inotropic effects of TNF-α were completely prevented by 'neutralizing concentrations' of TNF-BPs, whereas lesser concentrations of TNF-BPs only partially attenuated the negative inotropic effects of TNF-α. 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-α. When cardiac myocytes that had been treated with TNF-α (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-α in vitro.
UR - http://www.scopus.com/inward/record.url?scp=0028898719&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.1995.268.2.h517
DO - 10.1152/ajpheart.1995.268.2.h517
M3 - Article
C2 - 7864177
AN - SCOPUS:0028898719
SN - 0363-6135
VL - 268
SP - H517-H525
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 2 37-2
ER -