title: Innate immune responses and neuroepithelial degeneration and regeneration in the mouse olfactory mucosa induced by intranasal administration of Poly(I:C).
abstract: The pathogenesis of postviral olfactory disorder (PVOD) has not been fully elucidated. We investigated morphological changes and innate immune responses in the mouse olfactory mucosa induced by intranasal administration of polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA. Mice received three administrations of saline with or without Poly(I:C), once every 24 h. The olfactory mucosa was harvested at various intervals after the first administration (8 h, 3, 9 and 24 days). In the Poly(I:C) group, the number of apoptotic cells in the olfactory neuroepithelium had increased at 8 h. At 9 days, the olfactory neuroepithelium had severely degenerated and behavioral tests demonstrated that the mice showed signs of olfactory deterioration. At 24 days, the structure of the neuroepithelium had regenerated almost completely. Regarding the innate immune responses, many neutrophils had infiltrated the olfactory neuroepithelium at 8 h and had exuded into the nasal cavity by 3 days. Macrophages had also infiltrated the olfactory neuroepithelium at 8 h although to a lesser extent, but they still remained in the neuroepithelium at 24 days. Poly(I:C)-induced neuroepithelial damage was significantly inhibited by a neutrophil elastase inhibitor and was suppressed in neutropenic model mice. These findings suggest that the secondary damage caused by the neutrophil-mediated innate immune response plays an important role in the pathogenesis of PVOD.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kanaya
authors.forename: Kenji
authors.initials: K
authors.lastname: Kondo
authors.forename: Keigo
authors.initials: K
authors.lastname: Suzukawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Shu
authors.initials: S
authors.lastname: Kikuta
authors.forename: Kazunari
authors.initials: K
authors.lastname: Okada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007150:Immunohistochemistry; D007369:Interferon Inducers / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000294:innervation; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011070:Poly I-C / Q000494:pharmacology*
chemical_list: D007369:Interferon Inducers; D010196:Pancreatic Elastase; D011070:Poly I-C
references.citation: J Neurosci. 2010 Feb 10;30(6):2324-9
references.pmid: 20147558
references.citation: Med Clin North Am. 1991 Nov;75(6):1321-53
references.pmid: 1943323
references.citation: Brain Res Dev Brain Res. 1994 Dec 16;83(2):209-15
references.pmid: 7697881
references.citation: J Neurosci Res. 1990 May;26(1):31-44
references.pmid: 2141653
references.citation: Chem Senses. 2002 Jul;27(6):521-7
references.pmid: 12142328
references.citation: Toxicol Appl Pharmacol. 2011 Jan 1;250(1):29-38
references.pmid: 20932985
references.citation: Nature. 2007 Nov 22;450(7169):503-8
references.pmid: 17989651
references.citation: J Neurosci. 1984 Mar;4(3):868-79
references.pmid: 6707736
references.citation: B-ENT. 2009;5 Suppl 13:97-107
references.pmid: 20084810
references.citation: J Comp Neurol. 2011 Aug 1;519(11):2154-74
references.pmid: 21452219
references.citation: Am J Respir Cell Mol Biol. 2003 Jun;28(6):731-7
references.pmid: 12600836
references.citation: Respir Res. 2009 Jun 01;10:43
references.pmid: 19486528
references.citation: Cell. 1993 Jul 30;74(2):309-18
references.pmid: 8343958
references.citation: Exp Lung Res. 2007 Mar;33(2):71-80
references.pmid: 17454103
references.citation: J Neurosci. 1992 Oct;12(10):3896-919
references.pmid: 1403089
references.citation: J Neurochem. 1975 Jun;24(6):1101-6
references.pmid: 805214
references.citation: Otolaryngol Head Neck Surg. 2008 Mar;138(3):334-9
references.pmid: 18312881
references.citation: Am J Respir Cell Mol Biol. 1993 Oct;9(4):455-62
references.pmid: 7691110
references.citation: Anat Rec. 1991 Nov;231(3):358-74
references.pmid: 1763818
references.citation: J Cell Biol. 1993 Nov;123(3):513-22
references.pmid: 8227122
references.citation: Acta Otolaryngol Suppl. 1998;538:191-6
references.pmid: 9879419
references.citation: J Neurosci Res. 2007 Feb 15;85(3):548-57
references.pmid: 17171702
references.citation: Virology. 1996 May 15;219(2):339-49
references.pmid: 8638399
references.citation: Antimicrob Agents Chemother. 1992 Jul;36(7):1352-7
references.pmid: 1324643
references.citation: Clin Exp Allergy. 2006 Aug;36(8):1049-62
references.pmid: 16911361
references.citation: Laryngoscope. 2011 Aug;121(8):1687-701
references.pmid: 21792956
references.citation: Chem Senses. 2009 Feb;34(2):171-9
references.pmid: 19091696
references.citation: J Gen Virol. 2002 Sep;83(Pt 9):2109-2116
references.pmid: 12185263
references.citation: J Clin Invest. 1990 Mar;85(3):682-9
references.pmid: 2107207
references.citation: Cell. 1993 May 7;73(3):597-609
references.pmid: 7683976
references.citation: Nature. 2001 Oct 18;413(6857):732-8
references.pmid: 11607032
references.citation: Toxicol Pathol. 1995 Jul-Aug;23(4):477-86
references.pmid: 7501959
references.citation: Adv Drug Deliv Rev. 2008 Apr 29;60(7):805-12
references.pmid: 18262679
references.citation: J Comp Neurol. 1989 Jul 8;285(2):246-61
references.pmid: 2760264
references.citation: J Exp Med. 2001 Sep 17;194(6):863-9
references.pmid: 11561001
references.citation: Toxicol Appl Pharmacol. 1988 Jun 30;94(2):311-28
references.pmid: 2455365
references.citation: Anat Rec. 2002 Feb 15;269(1):33-49
references.pmid: 11891623
references.citation: Adv Immunol. 2001;78:1-56
references.pmid: 11432202
references.citation: Trends Immunol. 2002 Nov;23(11):549-55
references.pmid: 12401408
references.citation: Annu Rev Med. 1985;36:207-16
references.pmid: 3888051
references.citation: Neuroscience. 1998 Mar;83(1):191-200
references.pmid: 9466409
references.citation: J Trauma. 2006 May;60(5):936-43; discussion 943
references.pmid: 16688053
references.citation: J Virol. 2012 Nov;86(21):11416-24
references.pmid: 22915814
references.citation: Cell Tissue Res. 2009 Mar;335(3):489-503
references.pmid: 19142664
references.citation: Cell Signal. 2009 Mar;21(3):448-56
references.pmid: 19121387
references.citation: Adv Otorhinolaryngol. 2006;63:125-132
references.pmid: 16733337
references.citation: Am J Otolaryngol. 1979 Fall;1(1):57-79
references.pmid: 399716
references.citation: J Comp Neurol. 1996 Dec 23;376(4):509-17
references.pmid: 8978466
references.citation: J Leukoc Biol. 2010 Jan;87(1):59-67
references.pmid: 20052800
references.citation: J Comp Neurol. 1998 Nov 2;400(4):469-86
references.pmid: 9786409
references.citation: Otolaryngol Clin North Am. 2004 Dec;37(6):1159-66
references.pmid: 15563908
references.citation: Biochem Biophys Res Commun. 2002 May 24;293(5):1364-9
references.pmid: 12054664
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G705-17
references.pmid: 11518683
references.citation: J Clin Invest. 1992 May;89(5):1478-84
references.pmid: 1569186
references.citation: Microsc Res Tech. 2002 Aug 1;58(3):168-75
references.pmid: 12203695
references.citation: Brain Res. 1983 Mar 7;262(2):303-8
references.pmid: 6839159
references.citation: Am J Respir Cell Mol Biol. 2004 Sep;31(3):358-64
references.pmid: 15191912
references.citation: J Comp Neurol. 1995 Aug 14;359(1):15-37
references.pmid: 8557844
references.citation: Otolaryngol Head Neck Surg. 1992 Feb;106(2):181-8
references.pmid: 1738551
references.citation: J Histochem Cytochem. 2002 Jul;50(7):961-72
references.pmid: 12070275
references.citation: J Infect Dis. 2008 Sep 1;198(5):664-72
references.pmid: 18662130
references.citation: Pharmacol Toxicol. 1995 Jan;76(1):76-9
references.pmid: 7753763
references.citation: J Neurocytol. 1979 Apr;8(2):197-213
references.pmid: 469573
references.citation: J Exp Med. 2005 May 16;201(10):1615-25
references.pmid: 15883173
references.citation: J Neurosci. 1989 Feb;9(2):683-91
references.pmid: 2918383
references.citation: Chem Senses. 2001 Oct;26(8):937-52
references.pmid: 11595671
references.citation: Eur J Immunol. 1981 Oct;11(10):805-15
references.pmid: 7308288
references.citation: Chem Senses. 2002 Oct;27(8):691-701
references.pmid: 12379593
references.citation: Chem Biol Interact. 2004 Apr 15;147(3):247-58
references.pmid: 15135081