CC Chemokine Receptor 2 is Protective Against Noise-Induced Hair Cell Death: Studies in CX3CR1+/GFP Mice

Sautter, Nathan B.; Shick, Elizabeth H.; Ransohoff, Richard M.; Charo, Israel F.; Hirose, Keiko

doi:10.1007/s10162-006-0051-x

Cited by 49 publications

(58 citation statements)

References 29 publications

(33 reference statements)

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“…Abundant leukocyte recruitment was observed in all three groups of bone marrow chimeras. monocyte migration in brain and spinal cord, appear not to be critical cues for monocyte migration in the ear (Sautter et al 2006).…”

Section: Discussionmentioning

confidence: 91%

Expression of Fractalkine Receptor CX3CR1 on Cochlear Macrophages Influences Survival of Hair Cells Following Ototoxic Injury

Sato

Shick

Ransohoff

et al. 2009

JARO

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112

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The role of innate immunity and macrophage recruitment to the inner ear after hair cell injury is a subject where little is known. In this paper, we demonstrate recruitment of monocytes and macrophages to the inner ear after kanamycin. We also examined the effect of fractalkine receptor (CX3CR1) deletion in kanamycin ototoxicity. We observed more functional and structural damage in CX3CR1 null mice compared to wild-type and heterozygous littermates. In order to determine if increased susceptibility to kanamycin resulted from CX3CR1 deletion from cochlear leukocytes, we created bone marrow chimeras by transplanting CX3CR1-null bone marrow into wild-type mice whose native bone marrow was ablated by lethal irradiation. These mice were then treated with kanamycin sulfate. Auditory brainstem responses (ABR), hair cell counts, and numbers of macrophages recruited to the cochlea were recorded in irradiated mice that received either wild-type, CX3CR1 heterozygous, or CX3CR1 knockout bone marrow. A strong correlation was present between numbers of macrophages and hair cell death in recipients transplanted with CX3CR1 null marrow. No correlation between macrophage number and hair cell loss was present in mice transplanted with wild-type or CX3CR1 heterozygous marrow. We suggest that CX3CR1 plays a role in modulating the detrimental effects of cochlear macrophages after kanamycin ototoxicity. Our data point to the possibility that CX3CR1-deficient cochlear macrophages exacerbate kanamycin ototoxicity while CX3CR1-expressing monocytes do not.

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Section: Discussionmentioning

confidence: 91%

Expression of Fractalkine Receptor CX3CR1 on Cochlear Macrophages Influences Survival of Hair Cells Following Ototoxic Injury

Sato

Shick

Ransohoff

et al. 2009

JARO

Self Cite

112

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“…CX3CR1 GFP/GFP male mice were acquired from The Jackson Laboratory and bred with C57Bl/6 females to produce CX3CR1 GFP/+ mice. These heterozygous mice have been used in previous studies of inner ear macrophages, which indicated that CX3CR1 GFP/+ mice have normal macrophage function in the inner ear and express GFP exclusively in macrophages (Hirose et al 2005;Sautter et al 2006;Sato et al 2008Sato et al , 2010.…”

Section: Cx3cr1 Gfp/+ Micementioning

confidence: 99%

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Baker

Roy

Brandon

et al. 2014

JARO

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Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin treatment include nephrotoxicity and ototoxicity. Cisplatin ototoxicity results from damage to and death of cells in the inner ear, including sensory hair cells. We showed previously that heat shock inhibits cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. Since heat shock protein 70 (HSP70) is the most upregulated HSP in response to heat shock, we investigated the role of HSP70 as a potential protectant against cisplatin-induced hair cell death. Our data using utricles from HSP70 −/− mice indicate that HSP70 is necessary for the protective effect of heat shock against cisplatin-induced hair cell death. In addition, constitutive expression of inducible HSP70 offered modest protection against cisplatin-induced hair cell death. We also examined a second heat-inducible protein, heme oxygenase-1 (HO-1, also called HSP32). HO-1 is an enzyme responsible for the catabolism of free heme. We previously showed that induction of HO-1 using cobalt protoporphyrin IX (CoPPIX) inhibits aminoglycoside-induced hair cell death. Here, we show that HO-1 also offers significant protection against cisplatin-induced hair cell death. HO-1 induction occurred primarily in resident macrophages, with no detectable expression in hair cells or supporting cells. Depletion of macrophages from utricles abolished the protective effect of HO-1 induction. Together, our data indicate that HSP induction protects against cisplatin-induced hair cell death, and they suggest that resident macrophages mediate the protective effect of HO-1 induction.

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“…This influx of monocytes initiates hours after cochlear injury and peaks at approximately 2–7 days after the initial damage (Fredelius, Rask-Andersen, 1990; Hirose et al, 2005; Tornabene et al, 2006; Wakabayashi et al, 2010). The infiltrated cells have been identified in various anatomic sites of the cochlea, with a marked accumulation in the spiral ligament, the scala tympani and the spiral limbus (Du et al, 2011; Hirose et al, 2005; Miyao et al, 2008; Sautter et al, 2006; Tornabene et al, 2006). In the spiral ligament, immune cells are present primarily in the region around fibrocytes (Hirose et al, 2005; Tornabene et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation

et al. 2015

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The immune response is an important component of the cochlear response to stress. As an important player in the cochlear immune system, the basilar membrane immune cells reside on the surface of the scala tympani side of the basilar membrane. At present, the immune cell properties in this region and their responses to stress are not well understood. Here, we investigated the functional role of these immune cells in the immune response to acoustic overstimulation. This study reveals that tissue macrophages are present in the entire length of the basilar membrane under steady-state conditions. Notably, these cells in the apical and the basal sections of the basilar membrane display distinct morphologies and immune protein expression patterns. Following acoustic trauma, monocytes infiltrate into the region of the basilar membrane, and the infiltrated cells transform into macrophages. While monocyte infiltration and transformation occur in both the apical and the basal sections of the basilar membrane, only the basal monocytes and macrophages display a marked increase in the expression of MHC II and CIITA, a MHC II production cofactor, suggesting the site-dependent activation of antigen-presenting function. Consistent with the increased expression of the antigen-presenting proteins, CD4+ T cells, the antigen-presenting partner, infiltrate into the region of the basilar membrane where antigen-presenting proteins are upregulated. Further pathological analyses revealed that the basal section of the cochlea displays a greater level of sensory cell damage, which is spatially correlated with the region of antigen-presenting activity. Together, these results suggest that the antigen-presenting function of the mononuclear phagocyte population is activated in response to acoustic trauma, which could bridge the innate immune response to adaptive immunity.

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CC Chemokine Receptor 2 is Protective Against Noise-Induced Hair Cell Death: Studies in CX3CR1+/GFP Mice

Cited by 49 publications

References 29 publications

Expression of Fractalkine Receptor CX3CR1 on Cochlear Macrophages Influences Survival of Hair Cells Following Ototoxic Injury

Expression of Fractalkine Receptor CX3CR1 on Cochlear Macrophages Influences Survival of Hair Cells Following Ototoxic Injury

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation

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