Exposure to hypoxia injures tracheal epithelium (ultrastructural study)

Abstract

270Airway epithelium performing one of the vital self-cleaning functions plays important role in the development of many disorders of the respiratory organs. It represents the first barrier to the inhaled injurants, it reacts promptly on the changes in the environment or on the therapeutic and diagnostic procedures (Konrádová, 1991). To our knowledge, only a few authors dealt with the effect of hypoxia on the structure of the epithelium lining rabbits' respiratory organs. A decrease in number of cells that belong to the diffuse neuroendocrine system was described after short exposure to environment with 13% O 2 in the tracheal epithelium of young rabbits (Echt et al., 1982). In alveolar epithelium, degranulation of the type II pneumocytes was recorded after 16 hours spent in a chamber with 8% O 2 (Réffy et al., 1977). We therefore decided to investigate the reaction of the lining epithelium of airways under hypoxic conditions. e experiments were performed in a chamber containing atmosphere with 10% O 2 , where air humidity was 100% and temperature reached 23°C. To demonstrate the isolated effect of normobaric hypoxia, the control animals were exposed to atmosphere with only increased humidity and temperature. MATERIAL AND METHODSIn our experiments, 9 SPF New Zealand White male rabbits (Charles River Deutschland, Sulzfeld, Germany) of body weight 1 500-3 000 g were used. ree animals served as untreated controls. ree animals (treated controls) were placed for 96 hours in a normobaric chamber containing normal atmosphere with 100% humidity and temperature 23°C. ree rabbits spent 96 hours under the same conditions, but the atmosphere in the experimental Exposure to hypoxia injures tracheal epithelium (ultrastructural study) ABSTRACT: e ultrastructure of the tracheal epithelium in rabbits exposed for 96 hours to normobaric hypoxia was studied. In rabbits placed for 96 hours in environment with increased temperature and humidity, the first phase of common response of goblet cells to injury, represented mostly by degeneration of the exhausted cells, was revealed. e decrease in O 2 concentration highly accelerated the reaction of the goblet cells. Due to the influence of high temperature, humidity and normobaric hypoxia, the second phase of the goblet cells' reaction, massive differentiation of new secretory elements accompanied with intraepithelial mucous glands' development, was recorded. In the ciliated cells, only mild signs of pathological alteration of deeper portions of their cytoplasm were noticed. In the area of the ciliary border, significant decrease in the number of kinocilia/µm 2 , increase in percentage of altered cilia and morphological signs of impairment of the vital self-cleaning ability were recorded.

Mild hyperoxia induces moderate pathological alteration in airway epithelium (ultrastructural study)

“…Massive differentiation of new secretory elements was initiated and resulted in apparent changes in goblet cells distribution accompanied with development of intraepithelial mucous glands. We observed similar reaction in animals exposed to normobaric hypoxia (Konradova et al, 2002). Compared with hyperoxia, even more advanced process of secretory cells reaction was encountered.…”

Consecutive Hypoxia Decreases Expression of NOTCH3, HEY1, CC10, and FOXJ1 via NKX2-1 Downregulation and Intermittent Hypoxia-Reoxygenation Increases Expression of BMP4, NOTCH1, MKI67, OCT4, and MUC5AC via HIF1A Upregulation in Human Bronchial Epithelial Cells

“…Long-term hypoxia has also been shown to regulate mucus secretion and arrangements of goblet cells as well as proliferation and differentiation of airway epithelial cells (Konrádová et al, 2002;Polosukhin et al, 2011;Leahy, 2012;Gerovac et al, 2014;Torres-Capelli et al, 2016). In vivo, consecutive exposure to 10% O 2 was reported to significantly increase proliferation of bronchial epithelial cells in mice, predominantly Clara cells, via the Hif2α−FoxM1−Relmα/β regulatory pathway, after 3 days of exposure (Torres-Capelli et al, 2016), while consecutive exposure to 10% O 2 for 4 days was shown to significantly increase the percentages of mucus-discharging and mucous gland-forming goblet cells in the tracheal epithelium in rabbits (Konrádová et al, 2002).…”

“…Long-term hypoxia has also been shown to regulate mucus secretion and arrangements of goblet cells as well as proliferation and differentiation of airway epithelial cells (Konrádová et al, 2002;Polosukhin et al, 2011;Leahy, 2012;Gerovac et al, 2014;Torres-Capelli et al, 2016). In vivo, consecutive exposure to 10% O 2 was reported to significantly increase proliferation of bronchial epithelial cells in mice, predominantly Clara cells, via the Hif2α−FoxM1−Relmα/β regulatory pathway, after 3 days of exposure (Torres-Capelli et al, 2016), while consecutive exposure to 10% O 2 for 4 days was shown to significantly increase the percentages of mucus-discharging and mucous gland-forming goblet cells in the tracheal epithelium in rabbits (Konrádová et al, 2002). In vitro, consecutive exposure of human bronchial epithelial cells in air-liquid interface (ALI) cultures to 1% O 2 for 14−28 days or to 0.5% O 2 for 21 days significantly decreased numbers of FOXJ1 + ciliated cells and increased numbers of MUC5AC + goblet cells (Polosukhin et al, 2011;Gerovac et al, 2014), while exposure to 5% O 2 for 6 − 12 h was sufficient to induce de-differentiation of murine airway epithelial cells in ALI cultures (Leahy, 2012).…”