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The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.ORCID iD: 0000-0002-7760-246x
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
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2019 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 9, article id 3181Article in journal (Refereed) Published
Abstract [en]

Background: The endolymphatic sac (ES) is endowed with a multitude of white blood cells that may trap and process antigens that reach the inner ear from nearby infection-prone areas, it thus serves as an immunologic defense organ. The human ES, and unexpectedly the rest of the inner ear, has been recently shown to contain numerous resident macrophages. In this paper, we describe ES macrophages using super-resolution structured fluorescence microscopy (SR-SIM) and speculate on these macrophages' roles in human inner ear defense.

Material and Methods: After ethical permission was obtained, human vestibular aqueducts were collected during trans-labyrinthine surgery for acoustic neuroma removal. Tissues were placed in fixative before being decalcified, rapidly frozen, and cryostat sectioned. Antibodies against IBA1, cytokine fractalkine (CX3CL1), toll-like receptor 4 (TLR4), cluster of differentiation (CD) 68, CD11b, CD4, CD8, and the major histocompatibility complex type II (MHCII) were used for immunohistochemistry.

Results: A large number of IBA1-positive cells with different morphologies were found to reside in the ES; the cells populated surrounding connective tissue and the epithelium. Macrophages interacted with other cells, showed migrant behavior, and expressed immune cell markers, all of which suggest their active role in the innate and adaptive inner ear defense and tolerance.

Discussion: High-resolution immunohistochemistry shows that antigens reaching the ear may be trapped and processed by an immune cell machinery located in the ES. Thereby inflammatory activity may be evaded near the vulnerable inner ear sensory structures. We speculate on the immune defensive link between the ES and the rest of the inner ear.

Place, publisher, year, edition, pages
2019. Vol. 9, article id 3181
Keywords [en]
human, cochlea, macrophages, IBA1, structured illumination microscopy
National Category
Otorhinolaryngology Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-377333DOI: 10.3389/fimmu.2018.03181ISI: 000457362000001PubMedID: 30774637OAI: oai:DiVA.org:uu-377333DiVA, id: diva2:1291408
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2024-01-17Bibliographically approved
In thesis
1. The Human Vestibular Aqueduct, Endolymphatic Duct and Sac: A Morphological Study Using Micro-CT, Super Resolution Immunohistochemistry and Synchrotron Phase Contrast Imaging
Open this publication in new window or tab >>The Human Vestibular Aqueduct, Endolymphatic Duct and Sac: A Morphological Study Using Micro-CT, Super Resolution Immunohistochemistry and Synchrotron Phase Contrast Imaging
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The inner ear lies sheltered in the temporal bone and consists of basically three parts: the cochlea (the hearing organ), the vestibular (the balance organ), and the endolymphatic duct (ED) and endolymphatic sac (ES). The ES and ED are located in a bony canal, the vestibular aqueduct (VA), located on the medial side of the vestibule. While the functions of the cochlea and the vestibular part of the inner ear are rather well studied, our knowledge of the function/s of the ES and ED remains limited and has intrigued scientists for centuries. Earlier studies have supported several theories, such as being an immune mediator, an aid in pressure regulation, related to the absorption of endolymph, and the production of endolymph.

 Otologic disorders, which affect both hearing and balance, such as Meniere’s disease (MD) and large vestibular aqueduct syndrome (LVAS), have been linked to dysfunction of the ES/ED. Studies of the human inner ear are fairly sparse. Research on the ES and ED have mainly been performed on animals, although both the anatomy and function may differ among various species.

This thesis aims to further investigate the anatomy and function of the human ES and ED with the two otologic disorders MD and LVAS in mind. To achieve this, we have used novel imaging techniques, such as super-resolution structured illumination microscopy (SR-SIM), micro-computerized tomography (micro-CT), and synchrotron radiation phase-contrast imaging (SR-PCI). The material used for imaging comes from different sources: human archival temporal bones from the Uppsala temporal bone collection; human fresh-frozen cadaveric bones from our collaborators at Western University, in London, Ontario, Canada; and fresh-frozen human ES harvested during vestibular schwannoma surgery after securing ethical permission.

The results of these studies describe the micro-anatomy of the VA, ED and ES down to a nanoscopic level. The discussion is based on the findings, relating them to earlier research with clinical implications regarding MD and LVAS.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 71
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1647
Keywords
Endolymphatic sac, endolymphatic duct, vestibular aqueduct, Meniere's disease, LVAS, micro-CT, synchrotron phase contrast imaging
National Category
Otorhinolaryngology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-406848 (URN)978-91-513-0901-9 (ISBN)
Public defence
2020-05-07, Enghoffsalen, Akademiska sjukhuset, Ing 50, Uppsala, 09:00 (Swedish)
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Available from: 2020-04-16 Created: 2020-03-13 Last updated: 2020-05-19

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Kämpfe Nordström, CharlottaDanckwardt-Lillieström, NiklasLaurell, GöranLiu, WeiRask-Andersen, Helge

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