Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae.

In the sensory epithelium, macrophages have been identified on the scala tympani side of the basilar membrane. These basilar membrane macrophages are the spatially closest immune cells to sensory cells and are able to directly respond to and influence sensory cell pathogenesis. While basilar membrane macrophages have been studied in acute cochlear stresses, their behavior in response to chronic sensory cell degeneration is largely unknown. Here we report a systematic observation of the variance in phenotypes, the changes in morphology and distribution of basilar membrane tissue macrophages in different age groups of C57BL/6J mice, a mouse model of age-related sensory cell degeneration. This study reveals that mature, fully differentiated tissue macrophages, not recently infiltrated monocytes, are the major macrophage population for immune responses to chronic sensory cell death. These macrophages display dynamic changes in their numbers and morphologies as age increases, and the changes are related to the phases of sensory cell degeneration. Notably, macrophage activation precedes sensory cell pathogenesis, and strong macrophage activity is maintained until sensory cell degradation is complete. Collectively, these findings suggest that mature tissue macrophages on the basilar membrane are a dynamic group of cells that are capable of vigorous adaptation to changes in the local sensory epithelium environment influenced by sensory cell status.

Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation.

The immune response is an important component of the cochlear response to stress. As an important player in the cochlear immune system, the basilar membrane immune cells reside on the surface of the scala tympani side of the basilar membrane. At present, the immune cell properties in this region and their responses to stress are not well understood. Here, we investigated the functional role of these immune cells in the immune response to acoustic overstimulation. This study reveals that tissue macrophages are present in the entire length of the basilar membrane under steady-state conditions. Notably, these cells in the apical and the basal sections of the basilar membrane display distinct morphologies and immune protein expression patterns. Following acoustic trauma, monocytes infiltrate into the region of the basilar membrane, and the infiltrated cells transform into macrophages. While monocyte infiltration and transformation occur in both the apical and the basal sections of the basilar membrane, only the basal monocytes and macrophages display a marked increase in the expression of major histocompatibility complex (MHC) II and class II transactivator (CIITA), a MHC II production cofactor, suggesting the site-dependent activation of antigen-presenting function. Consistent with the increased expression of the antigen-presenting proteins, CD4(+) T cells, the antigen-presenting partner, infiltrate into the region of the basilar membrane where antigen-presenting proteins are upregulated. Further pathological analyses revealed that the basal section of the cochlea displays a greater level of sensory cell damage, which is spatially correlated with the region of antigen-presenting activity. Together, these results suggest that the antigen-presenting function of the mononuclear phagocyte population is activated in response to acoustic trauma, which could bridge the innate immune response to adaptive immunity.

[Cochlear and retrocochlear deafness induced by immunity with different inner ear tissue antigens].

OBJECTIVES: To inquire into whether the different inner ear tissue antigens could cause different kind of hearing loss, and to find out the disorder positions of auditory system. METHODS: The basilar membrane (BM), spiral ligament (SL), and spiral ganglion (SG) of guinea pigs were removed for making antigens, respectively. Then, we used these antigens to immune guinea pigs. The special humour and cellular immune reaction, hearing function, and inner ear histopathological changes were observed. RESULTS: In BM-antigen and SL-antigen immune group, the various degrees of cochlear microphonic potential disturbance, recruitment, and immune pathological inflammation in cochlear duct and stria vascularis were found. In SG-antigen immune group, auditory nerve compound action potential changes were prominent, and the inner ear pathological damage mainly existed in cochlear axis vessels or surround areas, and SG. CONCLUSIONS: It was confirmed that the inner ear antigens come from different part of auditory system, which could cause cochlear or retrocochlear autoimmune disease.

The localization and specificity of guinea pig inner ear antigenic epitopes.

In this study, we investigated the relative localization of some antigenic epitopes in the inner ear. The inner ear protein antigens were extracted from various parts of the guinea pig inner ear. Brain, kidney, lung, heart and liver extracts were also obtained. We found by SDS-polyacrylamide gel electrophoresis that total inner ear extracts separated into three high concentration polypeptide bands with molecular weights of approximately 30, 42, 58 kd and three low density bands of 20, 25 and 35 kd. The 30 kd band was found mainly in the extract of the spiral ganglion and the acoustic nerve in the modiolus. The 42 and 58 kd bands were detected in the extract of the spiral ligament and the stria vascularis. The Organ of Corti and the basilar membrane extract gave rise to three bands of 30, 42 and 58 kd. Twenty-eight of the 75 sera from patients with inner ear disease reacted with the 30 and 58 kd bands of the inner ear protein extracts by immunoblotting. Sixteen of these 28 positive sera were then used to probe immunoblots of the brain, kidney, lung, heart and liver extracts. The 58 kd band was also found in protein extracts of the brain, the lung and the liver. This study suggests that the 30 kd antigenic epitope may be mainly related to the acoustic nerve and that the 58 kd antigenic epitope is not cochlear specific.

Fibronectin-like immunoreactivity of the basilar membrane of celloidin-embedded human temporal bone sections.

Dysfunction of the mechanical properties of the basilar membrane is a potential cause of presbycusis. In cases of minimal sensorineural or strial degeneration it is believed to play a major role. The membrane has been shown to be partly composed of fibronectin. Fibronectin immunoreactivity is diminished in aged rats. Mesothelial cell line the perilymphatic surface of the membrane and are reduced in number in the aged rat cochlea. Fibronectin immunoreactivity was examined in human temporal bone sections (6 months to 92 years old). Hematoxylin and eosin stained section (17 to 97 years) were immunoreactivity was demonstrable in the human cochlea, but was not reduced, even in the eldest cases examined The number of mesothelial cells was reduced, however, and was related to the age of the individual, but not to the clinical diagnosis or audiogram shape. These two factors do not, therefore, appear to give rise to hearing losses associated with presbycusis.

Predictive value of laboratory tests in "autoimmune" inner ear disease: preliminary report.

The purpose of this prospective, controlled study was to estimate the prevalence of immune-mediated (autoimmune) inner ear disease in a high-risk patient population, in order to determine the predictive value of a positive lymphocyte transformation test. The high-risk group was defined as any dizzy patient with unilateral or bilateral-asymmetric sensorineural hearing loss, who had not previously received immunotherapy. From more than 400 consecutive patients with a chief complaint of dizziness, 58 were entered into the study over an 8-month period. The control group consisted of 15 normal volunteers. Thirteen patients (22%) one control (7%) had positive lymphocyte transformation tests. The data suggest that positive results in "high-risk" patients are more common than previously believed. Assuming test sensitivity is 96%, specificity 93%, and disease prevalence 22% in high-risk patients, the predictive value of a positive lymphocyte transformation test using inner ear membranes is 79%. That is, approximately three fourths of all positive results are true positives. Positive results in suspected patients, therefore, should be considered true positives, and treatment recommended. Future research should attempt to refine the putative antigen(s), further define "high risk" patients, and prospectively verify these preliminary results.

[The role of several simultaneously acting mechanisms in the formation of the clinical symptomatology of Goodpasture's syndrome]. / Die Rolle mehrerer gleichzeitig wirkender allergischer Mechanismen in der Gestaltung der klinischen Symptomatologie vom Goodpasture Syndrom

Two cases of Goodpasture syndrome in young patients are described; the importance of a detailed analysis of the symptoms is stressed and found useful in explaining the origin of simultaneous manifestations of allergic reactions of different mechanisms. Thus a wider variety of therapeutical possibilities may be applied and better allowance made for the nature of diseases. An analogy is assumed between the occurrence of the symptoms described and of the development of auto-immune diseases which have not, or only with difficulty, been differentiated.