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Pathogenetic Mechanism of Olfactory Cell Injury after Exposure to Sulfur Dioxide in Mice
Author(s) -
Min YangGi,
Kim JeongWhun,
Hong SeokChan,
Dhong HunJong,
Jarin Peter R.,
Jin Yulian
Publication year - 2003
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200312000-00020
Subject(s) - neuroepithelial cell , olfactory marker protein , proliferating cell nuclear antigen , immunohistochemistry , western blot , pathology , biology , olfactory epithelium , olfactory system , microbiology and biotechnology , immunology , medicine , neuroscience , biochemistry , stem cell , neural stem cell , gene
Objectives This study aimed to investigate the cellular pathogenetic mechanism involved in olfactory tissue injury and regeneration. Study Design Adult male mice were exposed to 40 ppm SO 2 for 2 hours. Methods The mice were sacrificed immediately, 4 hours, and 1, 3, 5, 7, 10, 14, and 21 days after exposure to SO 2 . Olfactory neuroepithelium and bulbs were harvested at the time of sacrifice. Western blot and immunohistochemical staining were performed. Results Injuries of the olfactory neuroepithelium were found 24 hours after exposure to SO 2 . The number of total olfactory neuroepithelial cells decreased after SO 2 exposure and recovered after 3 weeks. In contrast, the number of proliferating cell nuclear antigen (PCNA)–positive cells increased after SO 2 injury and then decreased. In the neuroepithelium, where PCNA expression increased, olfactory marker protein (OMP)–positive cells were sparse. The expression of inducible nitric oxide synthase (iNOS) was localized in the lateral half of the turbinates. However, there was no expression of iNOS in the medial half of the turbinates, in which PCNA was strongly expressed. There was increased immunoreactivity of neuronal NOS (nNOS) in the surviving cells after SO 2 exposure. Immediately after exposure to SO 2 , the immunoreactivity to phosphorylated fraction of extracellular signal‐regulated kinases (phospho‐ERK)‐1/2 increased in the cytoplasm and nucleus of supporting cells. In Western blot analysis, nNOS expression increased 4 hours after SO 2 exposure. Conclusions These findings suggest that the regenerative activity of the neuroepithelium might be well demonstrated by PCNA immunoreactivity and that regeneration of the neuroepithelium can be activated several days after SO 2 injury. The two NOS isoforms, iNOS and nNOS, might contribute to neuroprotection in the olfactory neuroepithelium.