Bone marrow‐derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea

Abstract

Immune-mediated inner ear disorder has been well established as a clinical entity; however, the innate immune system of the inner ear is a poorly understood area of research with high clinical and immunological importance. Although the presence of resident tissue macrophages in the inner ear has been suggested, there has been some controversy. In this study, we analyzed the origin of cochlear resident macrophages and the contribution of hematopoietic bone marrow (BM) to the recruitment of macrophages in the cochlea. To visualize the localization of BM-derived cells, BM chimeric mice were made by transplantation of hematopoietic stem cells, which were genetically labeled with enhanced green fluorescent protein, into lethally irradiated C57BL/6 mice. The distribution and characteristics of BM-derived cells in the mouse cochlea were studied immunohistochemically. We successfully identified the constitutive presence of tissue resident macrophages in the spiral ligament and spiral ganglion that are derived from BM in larger numbers than previously reported. Moreover, cochlear resident macrophages gradually turn over for several months during steady-state replacement by BM-derived cells, and the number of cochlear macrophages immediately increased in response to local surgical stress. The present findings demonstrate the hematopoietic origin of cochlear resident and infiltrating macrophages. Our study provides a novel anatomical and immunological basis for the inner ear and indicates that the cochlear resident macrophages would be a therapeutic target in inner ear disorders.

Effects of Hyperbaric Oxygen and Dexamethasone on Proinflammatory Cytokines of Rat Cochlea in Noise-Induced Hearing Loss

“…TNF-> is known to cause accumulation of proinflammatory cells in the cochlea (8). Suppression of infiltration of these cells with inhibition of TNF-> signal was shown to reduce hearing loss in animal models (9).…”

Roles of prostaglandin E2 in the cochlea

“…However, recent studies indicate importance of the spiral ligament in the immune reaction in the cochlea. Macrophages and/or microglia are constitutively present in the spiral ligament and accumulate in response to injury (Hirose et al, 2005;Okano et al, 2008;Sato et al, 2008). The spiral ligament fibrocytes produce cytokines in response to exposure to bacterial toxins (Moon et al, 2006(Moon et al, , 2007 and noise exposure (Fujioka et al, 2006).…”

Changes in Proinflammatory Cytokines in the Cochlea in Relation to Hearing Thresholds in Noise-Exposed Rats

“…One of the mechanisms of secondary damage might be a local increase in the inflammatory response and proinflammatory cytokines because these cytokines rise endogenously in the first 2 weeks after noise exposure, which in turn increases inflammatory cell infiltration [8,11] .…”

“…An emphasis on the roles of the cytokines may enable us to understand changes in hearing in association with changes in cytokine levels. TNF-α accumulates proinflammatory cells in the cochlea [11] . It was experimentally shown that the inhibition of TNF-α and suppression of inflammatory cells reduced hearing loss [4] .…”