Loss of CX3CR1 augments neutrophil infiltration into cochlear tissues after acoustic overstimulation
Autor: | Ashu Sharma, Mitchell D. Frye, Richard Salvi, Bo Hua Hu, Celia Zhang, Juliana Riordan, Wei Sun, Senthilvelan Manohar |
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Rok vydání: | 2021 |
Předmět: |
Neutrophil clearance
Hearing loss CX3C Chemokine Receptor 1 Stimulation Acoustics Biology medicine.disease Cochlea Cell biology Mice Inbred C57BL Mice Cellular and Molecular Neuroscience Immune system Hearing Loss Noise-Induced Neutrophil Infiltration CX3CR1 otorhinolaryngologic diseases medicine Animals sense organs medicine.symptom Infiltration (medical) Noise-induced hearing loss |
Zdroj: | Journal of Neuroscience Research. 99:2999-3020 |
ISSN: | 1097-4547 0360-4012 |
Popis: | The cochlea, the sensory organ for hearing, has a protected immune environment, segregated from the systemic immune system by the blood-labyrinth barrier. Previous studies have revealed that acute acoustic injury causes the infiltration of circulating leukocytes into the cochlea. However, the molecular mechanisms controlling immune cell trafficking are poorly understood. Here, we report the role of CX3CR1 in regulating the entry of neutrophils into the cochlea after acoustic trauma. We employed B6.129P-Cx3cr1tm1Litt /J mice, a transgenic strain that lacks the gene, Cx3cr1, for coding the fractalkine receptor. Our results demonstrate that lack of Cx3cr1 results in the augmentation of neutrophil infiltration into cochlear tissues after exposure to an intense noise of 120 dB SPL for 1 hr. Neutrophil distribution in the cochlea is site specific, and the infiltration level is positively associated with noise intensity. Moreover, neutrophils are short lived and macrophage phagocytosis plays a role in neutrophil clearance, consistent with typical neutrophil dynamics in inflamed non-cochlear tissues. Importantly, our study reveals the potentiation of noise-induced hearing loss and sensory cell loss in Cx3cr1-/- mice. In wild-type control mice (Cx3cr1+/+ ) exposed to the same noise, we also found neutrophils. However, neutrophils were present primarily inside the microvessels of the cochlea, with only a few in the cochlear tissues. Collectively, our data implicate CX3CR1-mediated signaling in controlling neutrophil migration from the circulation into cochlear tissues and provide a better understanding of the impacts of neutrophils on cochlear responses to acoustic injury. |
Databáze: | OpenAIRE |
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