title: Primary biliary cirrhosis. Study of the action of mitochondrial antibody plus complement on mitochondrial membrane functions.
abstract: 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.
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D003165:Complement System Proteins; D006801:Humans; D007111:Immunity, Cellular; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008566:Membranes; D008928:Mitochondria; D008930:Mitochondria, Liver / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D008933:Mitochondrial Swelling; D010085:Oxidative Phosphorylation; D011817:Rabbits / Q000276:immunology; D051381:Rats
chemical_list: D000906:Antibodies; D003165:Complement System Proteins; D000251:Adenosine Triphosphatases