Pathological mechanisms in experimental autoimmune myasthenia gravis. I. Immunogenicity of syngeneic muscle acetylcholine receptor and quantitative extraction of receptor and antibody-receptor complexes from muscles of rats with experimental automimmune myasthenia gravis.
Pathological mechanisms in experimental autoimmune myasthenia gravis. I. Immunogenicity of syngeneic muscle acetylcholine receptor and quantitative extraction of receptor and antibody-receptor complexes from muscles of rats with experimental automimmune myasthenia gravis.
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DOI：
10.1084/jem.144.3.726
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发表时间：
1976-09-01
期刊：
影响因子：
--
通讯作者：
Seybold ME
中科院分区：
文献类型：
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作者：
Lindstrom JM;Einarson BL;Lennon VA;Seybold ME
用电鳗电器官或同系大鼠肌肉纯化的乙酰胆碱受体（AChR）免疫Lewis大鼠诱导实验性自身免疫性重症肌无力（EAMG）。虚弱的临床症状和神经肌肉传递受损的肌电图证据证明了这一点。诱导自身免疫反应所需的大鼠AChR量与鳗鱼所需的AChR量相当。大鼠AChrR与抗体的体外络合降低了其免疫原性。血清中存在肌AChR自身抗体，并与肌中AChR络合。抗体未与AChR的ACh结合位点结合，因为从肌肉中提取的抗体-AChR复合物仍能与125i - α -兔骨毒素结合。EAMG大鼠肌肉中AChR的提取量减少。用鳗鱼AChR免疫后，每隔一段时间测量肌肉中AChR和抗体-AChR复合物的量。急性EAMG大鼠的AChR含量下降，缓解期短暂升高至正常值以上，慢性EAMG大鼠的AChR含量最终下降至正常值的20%左右。在患有慢性EAMG的动物中，至少一半的AChR与抗体络合。因此，乙酰胆碱受体数量的减少和抗体-乙酰胆碱受体复合物的形成都有助于EAMG大鼠神经肌肉传递的损害。讨论了AChR含量变化的可能机制。
Immunization of Lewis rats with acetylcholine receptor (AChR) purified from either Electrophorus electricus electric organ or syngeneic rat muscle induced experimental autoimmune myasthenia gravis (EAMG). This was demonstrated by clinical signs of weakness and by electromyographic evidence of imparied neuromuscular transmission. The amount of rat AChR required to induce an autoimmune response was comparable to the amount of eel AChR required. In vitro complexing of rat AChrR with antibody reduced its immunogenicity. Autoantibody to muscle AChR was present in serum and complexed with AChR in muscle. Antibody was not bound to the ACh binding site of AChR, since antibody-AChR complexes extracted from muscle could still bind 125I-alpha-bungarotoxin. The amount of AChR extracted from muscle of rats with EAMG was diminished. The amount of AChR and antibody-AChR complexes in muscle was measured at intervals after immunization with eel AChR. The amount of AChR decreased in rats with acute EAMG, then transiently increased to more than normal amounts during remission, and finally decreased to only about 20% of normal in rats with chronic EAMG. At least half of the AChR remaining in animals with chronic EAMG was complexed with antibody. Thus, both a decrease in amount of AChR and the formation of antibody-AChR complexes contribute to impairment of neuromuscular transmission in rats with EAMG. The possible mechanisms involved in the changes in AChR content are discussed.