Subject(s)
Gestational Age , Lung Injury , Papio , Respiratory Tract Infections/complications , Animals , Bronchopulmonary Dysplasia/complications , Bronchopulmonary Dysplasia/etiology , Bronchopulmonary Dysplasia/microbiology , Bronchopulmonary Dysplasia/physiopathology , Disease Models, Animal , Humans , Infant, Newborn , Oxygen , Pseudomonas Infections , Pseudomonas aeruginosa/isolation & purification , Respiratory Tract Infections/microbiology , Staphylococcal Infections , Staphylococcus epidermidis/isolation & purificationABSTRACT
Experimental autoimmune myasthenia gravis (EAMG) was induced in rats by injection of purified acetylcholine receptor (AChR). In addition to detecting elevated serum titers of anti-AChR antibodies, we observed decreased twitch-tension at submaximal stimulation voltages and increased curare sensitivity by muscles obtained from immunized rats when compared to muscles obtained from nonimmune control rats. Furthermore, antibody-induced neuromuscular impairment was expressed to differing extents dependent on whether the diaphragm, soleus, or extensor digitorum longus muscle was examined. Thus, we conclude that potential antibody perturbation of AChR function will depend not only on the nature of the antibody, but also on the complex structure-function relationships that exist in individual muscles. This may partially explain the variable impairment of different muscle groups in patients with myasthenia.
Subject(s)
Muscle Contraction , Myasthenia Gravis/physiopathology , Receptors, Cholinergic/immunology , Animals , Antibodies/immunology , Antibody Formation , Female , Immunization , Muscle Contraction/drug effects , Rats , Rats, Inbred Lew , Tubocurarine/pharmacologyABSTRACT
Purified acetylcholine receptor (AChR) covalently coupled to the catalytically toxic A chain of ricin has been used to selectively eliminate rat lymph node cells involved in in vitro anti-AChR antibody responses. The resulting inhibition was specific in view of the lack of such inhibition of anti-Keyhole limpet hemocyanin antibody responses. Furthermore, when fractionated B cell or T cell populations were treated with AChR-A chain, both populations were found to be sensitive to the specific cytotoxicity. However, T cell cytotoxicity required higher concentrations of the immunotoxin. Furthermore, when AChR-immune lymphocytes were treated with AChR-A chain in vitro, they became unable to mediate secondary adoptive transfer responses in vivo. The abrogation of the anti-AChR adoptive response correlated with the lack of muscle weakness characteristic of experimental autoimmune myasthenia gravis. Thus, it is possible, in principle, to eliminate clones of antigen-reactive lymphocytes with antigen-ricin A chain immunotoxins. This lets open the possibility of using such agents in immunotherapeutic approaches to autoimmune disease.
