Expression of fractalkine receptor CX3CR1 on cochlear macrophages influences survival of hair cells following ototoxic injury.
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.
Sato
Eisuke
E
Department of Otolaryngology, Nagoya University, Nagoya, Japan.
Shick
H Elizabeth
HE
Ransohoff
Richard M
RM
Hirose
Keiko
K
D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D001853:Bone Marrow; D000073883:CX3C Chemokine Receptor 1; D002470:Cell Survival / Q000502:physiology; D003051:Cochlea / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D018072:Hair Cells, Auditory, Outer / Q000166:cytology* / Q000187:drug effects; D034381:Hearing Loss / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007612:Kanamycin / Q000633:toxicity*; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D011828:Radiation Chimera; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism
D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D011500:Protein Synthesis Inhibitors; D019707:Receptors, Chemokine; D007612:Kanamycin