Macrophage and microglia-like cells in the avian inner ear

Bhave, Sujata A.; Oesterle, Elizabeth C.; Coltrera, Marc D.

doi:10.1002/(sici)1096-9861(19980824)398:2<241::aid-cne6>3.0.co;2-0

Cited by 77 publications

(81 citation statements)

References 85 publications

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“…Upon activation of these receptors by TNFA or Fas (both paracrines secreted by inflammatory cells), pro-caspase-8 molecules are attracted to and cluster at the receptor level to allow for autocleavage and thus activation. Macrophages and other as-yet-unspecified inflammatory cells normally reside within the auditory SE (Warchol 1997;Bhave et al 1998). Within hours of aminoglycoside exposure, their numbers increase, especially in areas of hair cell lesions (Warchol 1997;Bhave et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages and other as-yet-unspecified inflammatory cells normally reside within the auditory SE (Warchol 1997;Bhave et al 1998). Within hours of aminoglycoside exposure, their numbers increase, especially in areas of hair cell lesions (Warchol 1997;Bhave et al 1998). Although their precise function(s) within the sensory organ remains unclear, these inflammatory cells may potentially promote hair cell degeneration by releasing TNFA, Fas, or other death receptor ligands.…”

Section: Discussionmentioning

confidence: 99%

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Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Cheng

Cunningham

Rubel

2003

JARO - Journal of the Association for Research in Otolaryngolog

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Caspases are a family of proteases that have been implicated as key mediators of cell death. Although nonspecific inhibition of caspase activation has been reported to prevent mammalian sensory hair cell death, the exact roles of individual caspases during hair cell death are unclear. In other systems, the activation of initiator caspases, such as caspase-8 and caspase-9, can lead to the activation of the effector caspase-3. We have begun to systematically characterize hair cell death in an in vitro system by examining the activation of these specific caspases in degenerating hair cells after acutely damaging the whole avian basilar papilla with gentamicin. Basilar papillae (BP) displayed a dose-dependent hair cell loss after a 24-h treatment with gentamicin at concentrations of 0.1, 0.5, and 2.0 mM. When treated with 0.5 mM gentamicin for 6, 12, or 24 h, hair cells first began to degenerate in the basal third of the BP and damage progressed apically. Supplementation of z-VAD-fmk, a general caspase inhibitor, provided short-term protection against gentamicin-induced hair cell death. Treatment with gentamicin for 6 or 12 h promoted the expression of active caspase-3 and active caspase-9 in many hair cells along the BP as shown by immunohistochemistry. At these timepoints, specific fluorescent-labeled peptide substrates detected more active caspase-3, caspase-8, and caspase-9 in gentamicin-treated hair cells relative to controls. Our data indicate that auditory hair cells degenerate as a result of gentamicin exposure in a caspase-dependent manner. Specifically, the upstream caspases, caspase-8 and caspase-9, and the downstream caspase-3 are activated in aminoglycoside-damaged hair cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Cheng

Cunningham

Rubel

2003

JARO - Journal of the Association for Research in Otolaryngolog

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“…In vivo, a few SCs in the BP enter S phase around 2 days after aminoglycoside treatment, and SC divi-sion peaks a day later (Bhave et al 1995(Bhave et al , 1998Stone et al 1999;Duncan et al 2006). To determine if SCs enter S phase on a similar schedule after streptomycin-induced HC damage in vitro, BrdU (1 µM) was added to culture media (DMEM/1% FBS) for 4 h at 1, 2, 3, 5, or 7 days in vitro, and cultures were fixed and immunolabeled for BrdU.…”

Section: Supporting Cell Reentry Into Cell Cycle After Aminoglycosidementioning

confidence: 99%

Supporting Cell Division Is Not Required for Regeneration of Auditory Hair Cells After Ototoxic Injury In Vitro

Shang

Cafaro

Nehmer

et al. 2010

JARO

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In chickens, nonsensory supporting cells divide and regenerate auditory hair cells after injury. Anatomical evidence suggests that supporting cells can also transdifferentiate into hair cells without dividing. In this study, we characterized an organ culture model to study auditory hair cell regeneration, and we used these cultures to test if direct transdifferentiation alone can lead to significant hair cell regeneration. Control cultures (organs from posthatch chickens maintained without streptomycin) showed complete hair cell loss in the proximal (high-frequency) region by 5 days. In contrast, a 2-day treatment with streptomycin induced loss of hair cells from all regions by 3 days. Hair cell regeneration proceeded in culture, with the time course of supporting cell division and hair cell differentiation generally resembling in vivo patterns. The degree of supporting cell division depended upon the presence of streptomycin, the epithelial region, the type of culture media, and serum concentration. On average, 87% of the regenerated hair cells lacked the cell division marker BrdU despite its continuous presence, suggesting that most hair cells were regenerated via direct transdifferentiation. Addition of the DNA polymerase inhibitor aphidicolin to culture media prevented supporting cell division, but numerous hair cells were regenerated nonetheless. These hair cells showed signs of functional maturation, including stereociliary bundles and rapid uptake of FM1-43. These observations demonstrate that direct transdifferentiation is a significant mechanism of hair cell regeneration in the chicken auditory after streptomycin damage in vitro.

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“…Degeneration of outer hair cells is the primary cause of hearing loss induced by aminoglycoside antibiotics (Browning et al 1982). Inflammatory cells have been identified in the avian inner ear and the mammalian cochlea, but it remains unclear whether the inflammatory cell population plays a role in repair or whether it propagates damage and participates in cellular injury after ototoxicity (Warchol 1997(Warchol , 1999Bhave et al 1998;Hirose et al 2005;Ladrech et al 2007;Sato et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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

Sato

Shick

Ransohoff

et al. 2009

JARO

103

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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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Macrophage and microglia-like cells in the avian inner ear

Cited by 77 publications

References 85 publications

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation

Supporting Cell Division Is Not Required for Regeneration of Auditory Hair Cells After Ototoxic Injury In Vitro

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

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