Airway epithelial cell changes in rats exposed to 0.25 ppm ozone for 20 months

Ito, Takaaki; Ikemi, Yoshiaki; Ohmori, Kaoru; Kitamura, Hitoshi; Kanisawa, Masayoshi

doi:10.1016/s0940-2993(11)80002-3

Cited by 14 publications

(5 citation statements)

References 31 publications

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“…Increases were reported for both PNECs and NEBs in a model of ozone-induced PNEC hyperplasia. 15 This is in contrast to previous work from our laboratory, using paraffin sections, 14 in which hyperplasia was characterized by increased numbers of NEBs; however, a trend toward increased numbers of solitary PNECs did not reach statistical significance, possibly due to insufficient sample size. PNECs are a rare cell type, and the use of the whole-mount preparation allowed us to identify more accurately a statistically significant increase in PNECs throughout all airway generations of the main axial path of the right middle lobe.…”

Section: Discussioncontrasting

confidence: 81%

Alteration of Pulmonary Neuroendocrine Cells during Epithelial Repair of Naphthalene-Induced Airway Injury

Peake

Reynolds

Stripp

et al. 2000

The American Journal of Pathology

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Whole-mount airway preparations isolated from the lungs of mice treated by intraperitoneal injection of naphthalene and allowed to recover for 5 days were examined for the distribution and abundance of solitary pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs) along the main axial pathway of the right middle lobe. Sham mice treated with corn oil vehicle were examined in a similar manner. An antibody to calcitonin gene-related peptide, a neuroendocrine cell marker, was used to identify the location, size, and number of PNECs and NEBs in the airways. After naphthalene treatment and epithelial repair, NEBs were significantly increased along the walls of the airways as well as on branch point ridges. The surface area covered by NEBs composed of 20 or fewer PNECs was significantly enlarged after naphthalene treatment compared with control NEBs of an equivalent cell number. The PNEC number per square millimeter was also increased more than threefold above control values after naphthalene treatment. These findings provide further support for a key role of neuroendocrine cells in the reparative process of airway epithelial cell renewal after injury.

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Section: Discussioncontrasting

confidence: 81%

Alteration of Pulmonary Neuroendocrine Cells during Epithelial Repair of Naphthalene-Induced Airway Injury

Peake

Reynolds

Stripp

et al. 2000

The American Journal of Pathology

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“…Experimentally induced hyperplasia of PNECs has been observed to occur in response to various toxic gases or carcinogenic stimuli [37]. Depending on the specific stimulus, the proliferative effect may be specifically restricted to a certain airway region [38,39]. PNEC proliferation was also seen in a number of non-neoplastic human lung diseases [37].…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cellsin vivo

Fehrenbach

Fehrenbach²,

Pan³

et al. 2002

Eur Respir J

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Keratinocyte growth factor-induced proliferation of rat airway epithelium is restricted to Clara cells in vivo. H. Fehrenbach, A. Fehrenbach, T. Pan, M. Kasper, R.J. Mason. #ERS Journals Ltd 2002. ABSTRACT: Keratinocyte growth factor (KGF) is a potent mitogen of pulmonary bronchial and alveolar epithelial cells. However, it is unclear which type(s) of airway epithelial cells (AEC) proliferate(s) in response to KGF.AEC proliferation was induced in rats by either endobronchial instillation of 5 mg recombinant human (rHu) KGF per kg body weight or by adenoviral transfer of the human KGF gene (Ad5-HuKGF). Alterations in terminal airway AEC were followed for up to 7 days after rHuKGF, and for up to 28 days after Ad5-HuKGF.Cell proliferation, as assessed by immunohistochemistry (IHC) for incorporated 5-bromo-29-deoxyuridine (BrdU) and quantified by stereology, peaked at days 1-2 and was resolved by day 7 after rHuKGF and by day 21 after Ad5-HuKGF. Double immunofluorescence labelling for BrdU or Ki-67 on the one hand, and for Clara cell specific protein 10 (CC10) and calcitonin-gene related peptide on the other hand, demonstrated that Clara cells, not pulmonary neuroendocrine cells, proliferated in response to human KGF. TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling) method in conjunction with IHC for MNF116 failed to detect significant numbers of apoptotic AEC. IHC in conjunction with stereology revealed transient phenotypic alterations with a decrease in CC10, an increase in surfactant protein D and an increase in CD44v6 in AEC.The authors conclude that Clara cells responded to human keratinocyte growth factor in vivo by proliferation as well as by changes in protein expression, whereas no significant response was observed in pulmonary neuroendocrine cells. As Clara cells are intimately involved in airway epithelial repair, ion and fluid transport, and modulate lung inflammation, the potential of human keratinocyte growth factor to protect the lung may in part rely on the response of Clara cells.

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“…Sunday and his colleague (Sunday and Willett, 1992), however, suggested that PNEC hyperplasia in the hamster model is a result of the differentiation from proliferative stem cells or from immature PNECs. Others showed that repair from airway injury is associated with PNEC hyperplasia and that proliferation contributes to this hyperplastic response (Ito et al, 1994;Stevens et al, 1997). A study investigating the role of PNEC-derived neuropeptides in lung development suggested that PNECs are involved in the regulation of epithelial renewal (Pan et al, 2002).…”

Section: Pulmonary Neuroendocrine Cells (Pnecs)mentioning

confidence: 99%