Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid–blood barrier
| Autor: | Fei Zhang, Min Dai, Manfred Auer, Xiaorui Shi, Wenjing Zhang, Dennis R. Trune, Lingling Neng, Jacqueline M. DeGagne, Ahmed M. Hassan, Anders Fridberger, Wenxuan He, Tianying Ren |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty Endocochlear potential Mice Transgenic Melanocyte Biology Tight Junctions Mice parasitic diseases medicine otorhinolaryngologic diseases Animals Humans Inner ear Cochlea Basement membrane Multidisciplinary Tight junction Macrophages Stria Vascularis Biological Sciences Cell biology medicine.anatomical_structure Cytoplasm Cell culture Ear Inner Melanocytes |
| Popis: | The microenvironment of the cochlea is maintained by the barrier between the systemic circulation and the fluids inside the stria vascularis. However, the mechanisms that control the permeability of the intrastrial fluid–blood barrier remain largely unknown. The barrier comprises endothelial cells connected to each other by tight junctions and an underlying basement membrane. In a recent study, we found that the intrastrial fluid–blood barrier also includes a large number of perivascular cells with both macrophage and melanocyte characteristics. The perivascular-resident macrophage-like melanocytes (PVM/Ms) are in close contact with vessels through cytoplasmic processes. Here we demonstrate that PVM/Ms have an important role in maintaining the integrity of the intrastrial fluid–blood barrier and hearing function. Using a cell culture-based in vitro model and a genetically induced PVM/M-depleted animal model, we show that absence of PVM/Ms increases the permeability of the intrastrial fluid–blood barrier to both low- and high-molecular-weight tracers. The increased permeability is caused by decreased expression of pigment epithelial-derived factor, which regulates expression of several tight junction-associated proteins instrumental to barrier integrity. When tested for endocochlear potential and auditory brainstem response, PVM/M-depleted animals show substantial drop in endocochlear potential with accompanying hearing loss. Our results demonstrate a critical role for PVM/Ms in regulating the permeability of the intrastrial fluid–blood barrier for establishing a normal endocochlear potential hearing threshold. |
| Databáze: | OpenAIRE |
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