Garcia Yvonne R, Pothitakis Jennifer C, Krolick Keith A
Department of Microbiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Clin Immunol. 2003 Feb;106(2):116-26. doi: 10.1016/s1521-6616(02)00023-2.
In an attempt to identify mechanisms that explain the difference in susceptibility of two rat strains to the induction of experimental autoimmune myasthenia gravis (EAMG), acetylcholine receptor (AChR)-reactive antibodies were tested for their ability to up-regulate levels of inducible nitric oxide synthase (iNOS) in skeletal muscles of disease-sensitive Lewis rats and disease-resistant Wistar Furth (WF) rats. Initially, the WF muscle cell line, WE1, appeared to be more sensitive to antibody-stimulated iNOS induction and NO production than did the Lewis muscle cell line, LE1. Next, AChR-reactive antibody induced widespread iNOS production in skeletal muscles of WF rats, while iNOS production in muscles of Lewis rats was much less pronounced. Finally, inhibition of iNOS activity by administration of a specific iNOS inhibitor resulted in increased susceptibility to the induction of impaired muscle function in EAMG-resistant WF rats. It is speculated that nitric oxide production plays a protective immunomodulating role in WF rats.
为了确定能够解释两种大鼠品系对实验性自身免疫性重症肌无力（EAMG）诱导易感性差异的机制，对乙酰胆碱受体（AChR）反应性抗体上调疾病敏感的Lewis大鼠和抗病的Wistar Furth（WF）大鼠骨骼肌中诱导型一氧化氮合酶（iNOS）水平的能力进行了测试。最初，WF肌肉细胞系WE1似乎比Lewis肌肉细胞系LE1对抗体刺激的iNOS诱导和NO产生更敏感。接下来，AChR反应性抗体在WF大鼠的骨骼肌中诱导广泛的iNOS产生，而Lewis大鼠肌肉中的iNOS产生则不那么明显。最后，通过给予特异性iNOS抑制剂抑制iNOS活性，导致抗EAMG的WF大鼠对诱导肌肉功能受损的易感性增加。据推测，一氧化氮的产生在WF大鼠中发挥着保护性免疫调节作用。
