Gulick T, Chung M K, Pieper S J, Schreiner G F, Lange L G
Department of Medicine, Jewish Hospital of St. Louis, Washington University Medical Center, Missouri 63110.
Biochem Biophys Res Commun. 1988 Jan 15;150(1):1-9. doi: 10.1016/0006-291x(88)90478-0.
We hypothesize that reversible depression of cardiac function in cardiac allograft rejection and lymphocytic myocarditis reflects down modulation of the beta-adrenergic receptor system by a soluble product of activated immune cells. Thus, exposure of cultured cardiac myocytes to mixed lymphocyte culture or activated splenocyte supernatants produces 70% inhibition of isoproterenol-stimulated cAMP concentrations (Ki = 5% supernatant) in the absence of gross cellular injury or control media effects. This cAMP suppressive factor is not dialyzable and is ammonium sulfate precipitable. Beta-adrenergic receptor density, binding constant and affinity states are unaffected. These results demonstrate the existence of a cytokine inhibitor of cAMP accumulation that may mediate, in part, depression of cardiac contractility observed when immune cells invade the myocardium.
我们推测，心脏同种异体移植排斥反应和淋巴细胞性心肌炎中心脏功能的可逆性抑制反映了活化免疫细胞的可溶性产物对β-肾上腺素能受体系统的下调作用。因此，在没有明显细胞损伤或对照培养基影响的情况下，将培养的心肌细胞暴露于混合淋巴细胞培养物或活化脾细胞上清液中，会使异丙肾上腺素刺激的环磷酸腺苷（cAMP）浓度受到70%的抑制（抑制常数Ki = 5%上清液）。这种cAMP抑制因子不可透析，可被硫酸铵沉淀。β-肾上腺素能受体密度、结合常数和亲和力状态不受影响。这些结果表明存在一种cAMP积累的细胞因子抑制剂，它可能部分介导了免疫细胞侵入心肌时观察到的心脏收缩力抑制。
