[Apoptosis in the immune response of inner ear].
OBJECTIVE
To investigate whether apoptosis is one of the mechanism in the immune response of inner ear,and to detect the expression of Fas, FasL, Bcl-2 and Bax in the inner ears.


METHODS
Sixteen healthy, female guinea pigs were employed in the experiment. Sensitized systematically with keyhole limpet hemocyanin (KLH), the KLH-immunized animals were inoculated with the same antigen, and the control animals were injected PBS through cochlea basal turn. The animals were sacrificed at 7 day after inner ear vaccination. Transmission electron microscopy was used to detect inner ear apoptotic cells, and paraffin sections of cochlea from animals were stained using a terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay to identify inner ear cells undergoing apoptosis. Immunohistochemistry method was used to detect the expression of Fas, FasL, Bcl-2 and Bax in the inner ears.


RESULTS
The observation of electron microscopy had shown the features characteristic of apoptotic cells in the KLH-immunized inner ears but not in the control inner ears. TUNEL-positive cells were found in the KLH-immunized inner ears but not in the control inner ears. The positive cells were the hair cells in Corti's organ, and the marginal cells in the stria vascularis and the neurons in the spiral ganglion. Moreover under morphological analysis by light microscope, these cells had the features characteristic of apoptosis. High expression of Fas and FasL could be detected in Corti's organ, the stria vascularis, the spiral ligament and the neurons of the spiral ganglion in the KLH-immunized inner ears. A low expression of Fas could be detected in the stria vascularis and the neurons of the spiral ganglion in the control inner ears, but no cells staining positive for FasL were found in the control inner ears. No cells staining positive for Bcl-2 were found in the KLH-immunized animals but moderate expression of Bcl-2 could be detected in Corti's organ, the lateral wall and the neurons of the spiral ganglion in the control inner ears. High expression of Bax could be detected in Corti's organ, the lateral wall and the neurons of the spiral ganglion in the KLH-immunized inner ears. A low expression of Bax could be detected in the neurons of the spiral ganglion and no cells staining positive for Bax were found in Corti's organ, the lateral wall in the control inner ears.


CONCLUSIONS
These findings suggest apoptosis is involved in the pathogenesis of the immune response of inner ear and Fas- FasL pathway is one of important signal transportation of the course and Bcl-2 and Bax have a critical role in the regulation of apoptotic cell death induced by the immune response of inner ear.
Xu
Li-Juan
LJ
Gong
Shu-Sheng
SS
Wang
Ji-Bao
JB
Huang
Xiang
X
Song
Peng
P
Yin
Shi-Hua
SH
Chen
Pei
P
Li
Hui
H
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D007758:Ear, Inner / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor