Muscle responds to an antibody reactive with the acetylcholine receptor by up-regulating monocyte chemoattractant protein 1: a chemokine with the potential to influence the severity and course of experimental myasthenia gravis.
Autoantibodies with reactivity against the postjunctional muscle receptor for acetylcholine receptor are able to interfere with contractile function of skeletal muscles and cause the symptoms of myasthenia gravis (MG) in humans, as well as in experimental animal models of MG. In the study described below using a rat model of MG, it was observed that exposure to acetylcholine receptor-reactive Abs also induced increased levels of chemokine (i.e., monocyte chemoattractant protein 1) production by skeletal muscle cells. This was true of both cultured rat myocytes exposed in vitro and rat muscle exposed in vivo following passive Ab transfer. Increased monocyte chemoattractant protein 1 production may explain the increased trafficking of leukocytes through muscle following Ab transfer described in this and other reports. These observations may also be relevant to the induction of disease symptoms in experimental animal models of MG, since numerous reports from this and other laboratories indicate that the cytokine environment provided by leukocytes trafficking through muscle may play a pivotal role in disease progression.
Department of Microbiology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Sara
S
Reyes-Reyna
Timothy
T
Stegall
Keith A
KA
Krolick
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D005260:Female; D007962:Leukocytes / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000209:etiology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology*; D017452:Receptors, IgG / Q000502:physiology; D015854:Up-Regulation
D000906:Antibodies; D018932:Chemokine CCL2; D011950:Receptors, Cholinergic; D017452:Receptors, IgG