SOLUBLE TNF BINDING-PROTEINS MODULATE THE NEGATIVE INOTROPIC PROPERTIES OF TNF-ALPHA IN-VITRO

被引:90
作者
KAPADIA, S
TORREAMIONE, G
YOKOYAMA, T
MANN, DL
机构
[1] VET ADM MED CTR, DEPT MED, CARDIOL SECT, HOUSTON, TX 77030 USA
[2] BAYLOR COLL MED, HOUSTON, TX 77030 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1995年 / 268卷 / 02期
关键词
CARDIAC MYOCYTE; CONTRACTILITY; CYTOKINE;
D O I
10.1152/ajpheart.1995.268.2.H517
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:H517 / H525
页数:9
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