Collagen molecules are major extracellular matrix proteins involved in the development and support of delicate auditory sensory organs. Type II collagen is widely distributed within inner ear tissues, while type IX is found only within the labyrinthine membrane and dense fibers of the tectorial membrane. Antibody specific for type II collagen has been shown to be elevated in some patients with hearing loss due to several presumably autoimmune illnesses (including Meniere's disease, otosclerosis, chronic progressive sensorineural hearing loss, and relapsing polychondritis). Purified human type II and LX collagens and an extract of human cochlear tissue were subjected to isolation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose. The sera of 21 patients with inner ear disease were examined for the presence of anticollagen and anticochlear antibodies; the sera were used to probe Western blots of purified human collagens U, LX, and XI, and cochlear protein extract with peroxidase-conjugated goat anti human polyvalent immunoglobulin as the second antibody. Anti-type II collagen antibodies were seen in 12 of 21 (57%) patients, while 13 of 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was found by SDS-PAGE of human cochlear tissue extracts, with 3 patients, all with Meniere's disease, having antibody activity to this protein detected by Western blot. Anti-type II and anti-type LX antibodies were found in a high percentage of patients with Meniere's disease, otosclerosis, and strial atrophy. Six patients (29%), and all control patients, had no detectable antibodies to these proteins by our assay.

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To better understand the role of immunocompetent cells in the defense mechanism of the upper respiratory tract against microbial invasions, the distribution patterns of those cells were investigated in nasal mucosa of mice maintained in three different conditions: germ-free (GF), specific pathogen-free (SPF), and conventional (CV) conditions. Immunostaining by the indirect peroxidase method and toluidine blue staining were employed for the detection of immunocompetent cells and mast cells. For immunostaining, anti-IgG, -IgA, and -IgM polyclonal antibodies and anti-Lyt-1, -Lyt-2, and -Mac-1 monoclonal antibodies were used as primary antibodies. In nasal mucosa of CV mice, Mac-1+ cells, mast cells, and all cell types of lymphocyte subsets were present. In nasal mucosa of SPF mice, all cell types were also positive, but fewer in number than those of CV mice. In nasal mucosa of GF mice, IgG+, IgA+, and Lyt-2+ cells were rare, although IgM+ and Lyt-1+ cells were present in small numbers. An electron microscopic study revealed that follicle-like lymphocyte aggregates with high endothelial venules were present in nasal mucosa close to the mucosal epithelia. These findings suggest that lymphocytes are mobilized to nasal mucosa, responding to continuous antigenic stimuli, and play an important role in the local defense mechanism of the upper respiratory tract.

We studied the shiverer mouse as a model for correcting hearing disorders resulting from genetic abnormalities of the central nervous system (CNS). Shiverer mice are homozygous for an autosomal recessive mutation (deletion) in the gene for myelin basic protein (MBP), a major protein component of the myelin sheath in the CNS. Under electron microscopic observation of the cochlear nerve, the CNS portion in shiverer mice showed hypomyelination, but the peripheral portion, including spiral ganglion cells, was normal. We produced MBP-transgenic mice by microinjection of an MBP cosmid clone into the pronucleus of fertilized eggs from shiverer mice. The transgenic mice were found to recover MBP levels up to 25% of normal. A greater number of axons in the transgenic mice were myelinated than in the shiverer mice, but the myelin sheath was not as thick as in normal controls. Every interpeak latency of brain stem auditory-evoked potentials was prolonged in the shiverer mice and improved in the transgenic mice. This study provides an example of gene therapy for hearing disorders caused by a CNS abnormality. We discuss some strategies for researching genetic hearing impairment or deafness in both animals and humans.

The ability of Streptococcus pyogenes to adhere to nasal mucosal cells was investigated by an in vitro assay system in order to clarify the actual role of secretory IgA in mucosal immunity in the nose. The number of bacteria adhering to isolated mucosal cells was significantly larger in patients with chronic sinusitis than in normal control subjects. The ability of bacteria to adhere, however, was significantly lower in the group of subjects having specific secretory IgA antibody activity to the M protein than in those having no secretory IgA activity. Findings demonstrated that mucosal immunity preventing or blocking the adherence of bacteria is impaired in patients with chronic sinusitis.