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Characterization and inflammatory response of perivascular-resident macrophage-like melanocytes in the vestibular
Fei Zhang1, Jinhui Zhang, Lingling Neng
1Oregon Hearing Research Center, NRC04, Department of Otolaryngology/Head and Neck Surgery, Oregon Health and Science University, Portland, OR, 97239, USA, zhangfe@ohsu.edu.
Abstract:
A large number of perivascular cells expressing both macrophage and melanocyte characteristics (named perivascular-resident macrophage-like melanocytes, PVM/Ms), previously found in the intra-strial fluid-blood barrier, are also found in the blood-labyrinth barrier area of the vestibular system in normal adult cochlea, including in the three ampullae of the semicircular canals (posterior, superior, and horizontal), utricle, and saccule. The cells were identified as PVM/Ms, positive for the macrophage and melanocyte marker proteins F4/80 and GSTα4. Similar to PVM/Ms present in the stria vascularis, the PVM/Ms in the vestibular system are closely associated with microvessels and structurally intertwined with endothelial cells and pericytes, with a density in normal (unstimulated) utricle of 225 ± 43/mm(2); saccule 191 ± 25/mm(2); horizontal ampullae 212 ± 36/mm(2); anterior ampullae 238 ± 36/mm(2); and posterior ampullae 223 ± 64/mm(2). Injection of bacterial lipopolysaccharide into the middle ear through the tympanic membrane causes the PVM/Ms to activate and arrange in an irregular pattern along capillary walls in all regions within a 48-h period. The inflammatory response significantly increases vascular permeability and leakage. The results underscore the morphological complexity of the blood barrier in the vestibular system, with its surrounding basal lamina, pericytes, as well as second line of defense in PVM/Ms. PVM/Ms may be important to maintain blood barrier integrity and initiating local inflammatory response in the vestibular system.
Insights
Perivascular-resident macrophage-like melanocytes (PVM/Ms) are found in the vestibular system
Area of Science:
- Inner ear biology
- Neuroscience
- Immunology
Background:
- Perivascular cells with dual macrophage and melanocyte markers (PVM/Ms) exist in the cochlear fluid-blood barrier.
- These PVM/Ms are also present in the vestibular system's blood-labyrinth barrier.
Purpose of the Study:
- To identify and characterize PVM/Ms in the vestibular system.
- To investigate the role of PVM/Ms in vestibular blood barrier integrity and inflammation.
Main Methods:
- Immunohistochemistry using macrophage (F4/80) and melanocyte (GSTα4) markers.
- Microscopic analysis of PVM/Ms association with microvessels in vestibular organs.
- Induction of inflammation via lipopolysaccharide injection to observe PVM/Ms activation and vascular changes.
Main Results:
- PVM/Ms were identified in the ampullae, utricle, and saccule of the normal adult cochlea.
- These cells are closely associated with microvessels, intertwined with endothelial cells and pericytes.
- LPS injection activated PVM/Ms, increasing vascular permeability and leakage, indicating an inflammatory role.
Conclusions:
- The vestibular system possesses a complex blood barrier including PVM/Ms as a second line of defense.
- PVM/Ms are crucial for maintaining vestibular blood barrier integrity.
- PVM/Ms play a role in initiating local inflammatory responses within the vestibular system.
