Fernández-Cruz E, Bootello A, Blanco M F, Gosálvez M, Segovia de Arana J M
Allergol Immunopathol (Madr). 1976 Mar-Apr;4(2):145-52.
It has been described that mitochondrial antibodies can be detected in the serum of primary biliary cirrhosis patients (over 90%) and that these antibodies are directed specifically against a component of the mitochondrial inner membrane. In the present study whole mitochondria isolated from rat liver were exposed to mitochondrial antibodies from patients with primary biliary cirrhosis, and to antibodies induced experimentally in rabbits to mitochondrial antigens of rat liver. This was an attempt to study the action of these antibodies and complement on mitochondrial functions. By studying respiratory control and oxidative phosphorylation of mitochondria, no significant, nor specific effect on mitochondrial membranes functions could be detected, after the incubation of suspensions of mitochdondria with normal or immune gamma-globulin (neither from rabbits nor from human) nor with the addition of complement. Furthermore, the respiration of fragmental mitochondria using succinate and NADH substrates was unaffected by the antibodies and complement. Similarly, mitochondrial APT-ase activity and swelling and contraction were not affected by antibody. Experiments are in progress to study the hypothesis of a lymphocyte dependent antibody mediated cytotoxicity in this system. In order to demonstrate that this autoimmune phenomenon might be associated with cellular immunity to a mitochondrial component, we have in a previous report demonstrated impairment of mitochondrial respiratory control by lymphocytes from rabbits sensitized in vivo with mitochondrial antigens. Subsequently we have recently shown evidence of sensitization. In-vivo of lymphocytes from patients with primary biliary cirrhosis as demonstrated by an injurious effect on rat liver mitochondria by lymphocytes from patients with this disease. Further studies are necessary to clarify the involvement of this phenomena in the possible mechanisms responsible for the pathogenesis of the lesions.
据描述，在原发性胆汁性肝硬化患者的血清中可检测到线粒体抗体（超过90%），且这些抗体特异性针对线粒体内膜的一种成分。在本研究中，将从大鼠肝脏分离的完整线粒体暴露于原发性胆汁性肝硬化患者的线粒体抗体以及实验诱导的兔抗大鼠肝脏线粒体抗原的抗体中。这是为了研究这些抗体和补体对线粒体功能的作用。通过研究线粒体的呼吸控制和氧化磷酸化，在线粒体悬浮液与正常或免疫γ球蛋白（既不是兔源也不是人源）孵育后，或添加补体后，未检测到对线粒体膜功能有显著的特异性影响。此外，使用琥珀酸和NADH底物的片段化线粒体的呼吸不受抗体和补体的影响。同样，线粒体ATP酶活性以及肿胀和收缩也不受抗体影响。正在进行实验以研究该系统中淋巴细胞依赖性抗体介导的细胞毒性假说。为了证明这种自身免疫现象可能与针对线粒体成分的细胞免疫有关，我们在之前的报告中证明，用线粒体抗原在体内致敏的兔淋巴细胞会损害线粒体的呼吸控制。随后我们最近显示了致敏的证据。原发性胆汁性肝硬化患者的淋巴细胞在体内致敏，表现为该疾病患者的淋巴细胞对大鼠肝脏线粒体有损伤作用。需要进一步研究以阐明这种现象在病变发病机制的可能机制中的参与情况。
