Myocyte production of nitric oxide in response to AChR-reactive antibodies in two inbred rat strains may influence disease outcome in experimental myasthenia gravis.
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.
Garcia
Yvonne R
YR
Department of Microbiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Pothitakis
Jennifer C
JC
Krolick
Keith A
KA
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured / Q000378:metabolism; D002999:Clone Cells / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease; D007116:Immunization, Passive; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D011950:Receptors, Cholinergic / Q000276:immunology*; D014101:Torpedo
D001323:Autoantibodies; D004791:Enzyme Inhibitors; D009124:Muscle Proteins; C090663:N(6)-(1-iminoethyl)lysine; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008239:Lysine