Inner ear DNA receptors in MRL/lpr autoimmune mice: potential 30 and 70 kDa link between autoimmune disease and hearing loss.
Inner ear function and systemic autoimmune disease were evaluated in the MRL/lpr mouse to determine their relationship with alterations in cell surface DNA receptors of 28-30 and 68-70 kDa size. Auditory brainstem response thresholds in the autoimmune disease mice were significantly elevated as early as 2 months of age when compared to MRL/++ controls. Hearing thresholds continued to rise with progression of the disease, manifested as increasing spleen weights, antinuclear (anti-DNA) antibodies, and serum immune complexes. Cochlear membranous labyrinth cells in the autoimmune mice bound less DNA, suggesting the DNA receptors were abnormally occupied by circulating antibodies. Western blots of a murine T-cell line probed with autoimmune mouse sera demonstrated reactivity to 28-30 and 68-70 kDa proteins after disease onset. It is hypothesized that cell surface DNA binding molecules could be masked or down-regulated by circulating antibodies in autoimmune disease. This interference with DNA receptor activity may be occurring within the inner ear and underlie the cochlear dysfunction seen in autoimmune sensorineural hearing loss.
Trune
D R
DR
Oregon Hearing Research Center (NRCO4), Department of Otolaryngology, Head and Neck Surgery, Oregon Health Sciences University, Portland 97201-3098, USA.
Kempton
J B
JB
Hefeneider
S H
SH
Bennett
R M
RM
D000704:Analysis of Variance; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000097:blood; D001309:Auditory Threshold / Q000502:physiology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D001667:Binding, Competitive; D015153:Blotting, Western; D002460:Cell Line; D003051:Cochlea / Q000166:cytology / Q000276:immunology; D003851:Deoxyribonucleases / Q000378:metabolism; D007758:Ear, Inner / Q000276:immunology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000209:etiology* / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008970:Molecular Weight; D009929:Organ Size / Q000502:physiology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; C033365:DNA receptor; D011956:Receptors, Cell Surface; D003851:Deoxyribonucleases