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Journal of the Association for Research in Otolaryngology

Published in:

01-06-2010

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

Authors: Eisuke Sato, H. Elizabeth Shick, Richard M. Ransohoff, Keiko Hirose

Published in: Journal of the Association for Research in Otolaryngology | Issue 2/2010

Abstract

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.

Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10:1538–1543CrossRefPubMed

Bhave SA, Oesterle EC, Coltrera MD (1998) Macrophage and microglia-like cells in the avian inner ear. J Comp Neurol 398:241–256CrossRefPubMed

Browning GG, Northrop R, Cortese R (1982) Selective destruction of the outer hair cells in the chinchilla. Clin Otolaryngol Allied Sci 7:3–9CrossRefPubMed

Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924CrossRefPubMed

Chen CS, Saunders JC (1983) The sensitive period for ototoxicity of kanamycin in mice: morphological evidence. Arch Otorhinolaryngol 238:217–223CrossRefPubMed

Cotter R, Williams C, Ryan L, Erichsen D, Lopez A, Peng H, Zheng J (2002) Fractalkine (CX3CL1) and brain inflammation: implications for HIV-1-associated dementia. J Neurovirology 8:585–598CrossRef

Cuadros MA, Santos AM, Martin-Oliva D, Calvente R, Tassi M, Marin-Teva JL, Navascues J (2006) Specific immunolabeling of brain macrophages and microglial cells in the developing and mature chick central nervous system. J Histochem Cytochem 54:727–738CrossRefPubMed

Denes A, Ferenczi S, Halasz J, Kornyei Z, Kovacs KJ (2008) Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse. J Cereb Blood Flow Metab 28:1707–1721CrossRefPubMed

Ehret G (1983) Peripheral anatomy and physiology II. In: Willott J (ed) The auditory psychobiology of the mouse. Springfield, IL: Charles C. Thomas, p 169–200

Forge A, Fradis M (1985) Structural abnormalities in the stria vascularis following chronic gentamicin treatment. Hear Res 20:233–244CrossRefPubMed

Fredelius L, Rask-Andersen H (1990) The role of macrophages in the disposal of degeneration products within the organ of corti after acoustic overstimulation. Acta Otolaryngol 109:76–82CrossRefPubMed

Goodyear RJ, Gale JE, Ranatunga KM, Kros CJ, Richardson GP (2008) Aminoglycoside-induced phosphatidylserine externalization in sensory hair cells is regionally restricted, rapid, and reversible. J Neurosci 28:9939–9952CrossRefPubMed

Harrison JK, Jiang Y, Chen S, Xia Y, Maciejewski D, McNamara RK, Streit WJ, Salafranca MN, Adhikari S, Thompson DA, Botti P, Bacon KB, Feng L (1998) Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci USA 95:10896–10901CrossRefPubMed

Henry KR, Chole RA, McGinn MD, Frush DP (1981) Increased ototoxicity in both young and old mice. Arch Otolaryngol 107:92–95PubMed

Hirose K, Discolo CM, Keasler JR, Ransohoff R (2005) Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma. J Comp Neurol 489:180–194CrossRefPubMed

Jabba SV, Oelke A, Singh R, Maganti RJ, Fleming S, Wall SM, Everett LA, Green ED, Wangemann P (2006) Macrophage invasion contributes to degeneration of stria vascularis in Pendred syndrome mouse model. BMC Med 4:37CrossRefPubMed

Jiang H, Sha SH, Forge A, Schacht J (2006) Caspase-independent pathways of hair cell death induced by kanamycin in vivo. Cell Death Differ 13:20–30CrossRefPubMed

Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW, Sher A, Littman DR (2000) Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20:4106–4114CrossRefPubMed

Ladrech S, Wang J, Simonneau L, Puel JL, Lenoir M (2007) Macrophage contribution to the response of the rat organ of Corti to amikacin. J Neurosci Res 85:1970–1979CrossRefPubMed

Lauro C, Di Angelantonio S, Cipriani R, Sobrero F, Antonilli L, Brusadin V, Ragozzino D, Limatola C (2008) Activity of adenosine receptors type 1 Is required for CX3CL1-mediated neuroprotection and neuromodulation in hippocampal neurons. J Immunol 180:7590–7596PubMed

Lee JE, Nakagawa T, Kim TS, Iguchi F, Endo T, Kita T, Murai N, Naito Y, Lee SH, Ito J (2004) Signaling pathway for apoptosis of vestibular hair cells of mice due to aminoglycosides. Acta Otolaryngol Suppl, pp 69–74

Limatola C, Lauro C, Catalano M, Ciotti M, Bertollini C, DiAngelantonio S, Ragozzino D, Eusebi F (2005a) Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity. J Neurosci 166:19–28

Limatola C, Lauro C, Catalano M, Ciotti MT, Bertollini C, Di Angelantonio S, Ragozzino D, Eusebi F (2005b) Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity. J Neuroimmunol 166:19–28CrossRefPubMed

Matsui JI, Haque A, Huss D, Messana EP, Alosi JA, Roberson DW, Cotanche DA, Dickman JD, Warchol ME (2003) Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo. J Neurosci 23:6111–6122PubMed

Nakagawa T, Kim TS, Murai N, Endo T, Iguchi F, Tateya I, Yamamoto N, Naito Y, Ito J (2003) A novel technique for inducing local inner ear damage. Hear Res 176:122–127CrossRefPubMed

Neumann J, Gunzer M, Gutzeit HO, Ullrich O, Reymann KG, Dinkel K (2006) Microglia provide neuroprotection after ischemia. FASEB J 20:714–716PubMed

Nguyen MD, D’Aigle T, Gowing G, Julien JP, Rivest S (2004) Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis. J Neurosci 24:1340–1349CrossRefPubMed

Noben-Trauth K, Zheng QY, Johnson KR (2003) Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss. Nat Genet 35:21–23CrossRefPubMed

Oesterle EC, Campbell S, Taylor RR, Forge A, Hume CR (2008) Sox2 and JAGGED1 expression in normal and drug-damaged adult mouse inner ear. J Assoc Res Otolaryngol 9:65–89CrossRefPubMed

Sato E, Shick HE, Ransohoff RM, Hirose K (2008) Repopulation of cochlear macrophages in murine hematopoietic progenitor cell chimeras: the role of CX3CR1. J Comp Neurol 506:930–942CrossRefPubMed

Sautter NB, Shick EH, Ransohoff RM, Charo IF, Hirose K (2006) CC chemokine receptor 2 is protective against noise-induced hair cell death: studies in CX3CR1(+/GFP) mice. J Assoc Res Otolaryngol 7:361–372CrossRefPubMed

So H, Kim H, Kim Y, Kim E, Pae HO, Chung HT, Kim HJ, Kwon KB, Lee KM, Lee HY, Moon SK, Park R (2008) Evidence that cisplatin-induced auditory damage is attenuated by downregulation of pro-inflammatory cytokines via Nrf2/HO-1. J Assoc Res Otolaryngol 9:290–306CrossRefPubMed

Tabuchi K, Pak K, Chavez E, Ryan AF (2007) Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair cell damage. Neuroscience 149:213–222CrossRefPubMed

Taleb M, Brandon CS, Lee FS, Lomax MI, Dillmann WH, Cunningham LL (2008) Hsp70 inhibits aminoglycoside-induced hair cell death and is necessary for the protective effect of heat shock. J Assoc Res Otolaryngol 9:277–289CrossRefPubMed

Taleb M, Brandon CS, Lee FS, Harris KC, Dillmann WH, Cunningham LL (2009) Hsp70 inhibits aminoglycoside-induced hearing loss and cochlear hair cell death. Cell Stress Chaperones 14:427–437CrossRefPubMed

Taylor RR, Nevill G, Forge A (2008) Rapid hair cell loss: a mouse model for cochlear lesions. J Assoc Res Otolaryngol 9:44–64CrossRefPubMed

Warchol ME (1997) Macrophage activity in organ cultures of the avian cochlea: demonstration of a resident population and recruitment to sites of hair cell lesions. J Neurobiol 33:724–734CrossRefPubMed

Warchol ME (1999) Immune cytokines and dexamethasone influence sensory regeneration in the avian vestibular periphery. J Neurocytol 28:889–900CrossRefPubMed

Wu WJ, Sha SH, McLaren JD, Kawamoto K, Raphael Y, Schacht J (2001) Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat. Hear Res 158:165–178CrossRefPubMed

Title: Expression of Fractalkine Receptor CX3CR1 on Cochlear Macrophages Influences Survival of Hair Cells Following Ototoxic Injury
Authors: Eisuke Sato
H. Elizabeth Shick
Richard M. Ransohoff
Keiko Hirose
Publication date: 01-06-2010
Publisher: Springer-Verlag
Published in: Journal of the Association for Research in Otolaryngology / Issue 2/2010
Print ISSN: 1525-3961
Electronic ISSN: 1438-7573
DOI: https://doi.org/10.1007/s10162-009-0198-3

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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