Number and Proliferation of Basal and Parabasal Cells in Normal Human Airway Epithelium

Boers, James E.; Ambergen, A.W.; Thunnissen, F.B.J.M.

doi:10.1164/ajrccm.157.6.9707011

Cited by 239 publications

(194 citation statements)

References 20 publications

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“…Along with these specific features of type II pneumocytes, we detected in some cells an expression of CK 5, that in lungs has only been described in basal cells (Stosiek et al , 1992;Barth et al, 2000). Such cells are considered to be progenitor cells of bronchi and large bronchioles (Boers et al, 1998). The cuboidal alveolar cells identified in the CF pulmonary tissue may represent cells at an intermediate stage of differentiation.…”

Section: Discussionsupporting

confidence: 50%

Growth of putative progenitors of type II pneumocytes in culture of human cystic fibrosis alveoli

Hollande

Cantet

Ratovo

et al. 2004

Biology of the Cell

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Alveolar type II pneumocytes are thought to be progenitor cells capable of self-renewal and differentiation into type I pneumocytes. Nevertheless, the existence of an alveolar stem cell has been postulated. In lungs from patients with cystic fibrosis, the alveolar epithelium is damaged with ulceration and subsequent regeneration. We characterized alveolar modifications histologically and immunohistochemically in the pulmonary tissue of a patient homozygous for the DF508 mutation. Alveoli were of variable size and surrounded by an inflammatory infiltrate. They were lined by a continuous layer of cuboidal cells with very weak proliferative activity. These cells resembled type II pneumocytes. They expressed thyroid transcription factor-1, cystic fibrosis transmembrane conductance regulator, cytokeratin 7 and contained lamellar bodies. Weak expression of cytokeratin 5 considered to be a marker of progenitor cells of the bronchial and bronchiolar epithelium was detected. Explantation of this alveolar epithelium produced primary cultures and subcultures of epithelial cells that had acquired proliferative properties showing signs of dedifferentiation with a loss of lamellar bodies and a lack of expression of thyroid transcription factor-1. Persistence of the expression of cytokeratin 7 and a strong expression of cytokeratin 5 were observed. The culture conditions were thought to have circumvented the inhibition of proliferation observed in vivo due to the inflammatory peri-alveolar environment. They thus favored the multiplication of a population of cells co-expressing cytokeratin 5 and certain characteristics of type II pneumocytes. The presence of these cells of intermediate phenotype is indicative of the existence of immature precursors for type II pneumocytes.

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Section: Discussionsupporting

confidence: 50%

Growth of putative progenitors of type II pneumocytes in culture of human cystic fibrosis alveoli

Hollande

Cantet

Ratovo

et al. 2004

Biology of the Cell

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“…Polarized airway epithelial cells have a relatively low rate of cell proliferation under healthy conditions, with less than 1% cell turnover. 28 Along with increased cell death, airway epithelial cell proliferation was increased in asthmatic airways as shown by increased immunopositivity for the proliferation marker MIB-1, detected with an antibody directed against part of the Ki-67 antigen (% MIB-1-positive: asthma, 19.7 Ϯ 2.5; controls, 1.8 Ϯ 0.2; Figure 2). …”

Section: Increased Apoptosis In Asthmatic Airway Epithelial Cellsmentioning

confidence: 98%

“…MIB-1, an antibody directed against recombinant parts of the Ki-67 antigen, 28 allows reliable determination of proliferating cells. 28 Endobronchial biopsies from asthmatic and control individuals were used for immunostaining.…”

Section: Immunohistochemical Analysis Of Mib-1mentioning

confidence: 99%

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Superoxide Dismutase Inactivation in Pathophysiology of Asthmatic Airway Remodeling and Reactivity

Comhair

Ghosh

et al. 2005

The American Journal of Pathology

175

149

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Airway hyperresponsiveness and remodeling are defining features of asthma. We hypothesized that impaired superoxide dismutase (SOD) antioxidant defense is a primary event in the pathophysiology of hyperresponsiveness and remodeling that induces apoptosis and shedding of airway epithelial cells. Mechanisms leading to apoptosis were studied in vivo and in vitro. Asthmatic lungs had increased apoptotic epithelial cells compared to controls as determined by terminal dUTP nick-end labeling-positive cells. Apoptosis was confirmed by the finding that caspase-9 and -3 and poly (ADP-ribose) polymerase were cleaved. On the basis that SOD inactivation triggers cell death and low SOD levels occur in asthma, we tested whether SOD inactivation plays a role in airway epithelial cell death. SOD inhibition increased cell death and cleavage/activation of caspases in bronchial epithelial cells in vitro. Asthma is commonly diagnosed using physiological measures, but alterations in airway structure are the defining features of asthma. Damage to airway epithelium, eosinophil infiltration, smooth muscle hyperplasia, thickening and aberrant collagen, and protein composition of the basement membrane are well established elements of the asthmatic airway. 1,2 The injury to the bronchial epithelium in asthma is marked by loss of columnar epithelial cells. Extensive loss of cells and denuded basement membrane with few basal cells remaining on the airway surface are noted in severe asthma, but shedding of airway epithelium is present even in clinically mild asthma. 2,3 Physical loss of epithelial lining cells is considered one proximate cause of the airway hyperresponsiveness to inhaled mediators, and has been speculated to contribute to asthmatic airway remodeling, in particular abnormal collagen synthesis. Evidence from organ culture systems supports the concept of an epithelial-mesenchymal unit in which loss of epithelium leads to mucosal myofibroblast and fibroblast proliferation, and collagen deposition. 2,4 -6 Thus, if the epithelial injury and loss could be understood and prevented in asthma, the clinical symptoms of airway hyperresponsiveness and long-term progressive sequelae in the airways, which contribute to fixed airflow limitation, might be prevented.Several reports have proposed that loss of epithelial cells is because of apoptosis based on immunostaining for the proteins that regulate apoptosis, or by detection of DNA strand breaks by immunostaining with the terminal dUTP nick-end labeling (TUNEL) assay. 7-11 However, not all reports have confirmed increased TUNEL positivity in airways. 9 Furthermore, if airway epithelial cells are undergoing increased cell death, it is unclear whether this is because of an inherent cell defect or a response to the asthmatic airway environment. Although nonspecific events related to increased levels of reactive oxygen and

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“…Both basal and nonciliated se-cretory cell types of bronchial airways have been shown to exhibit proliferative capacity. 8,9,11,12,20,21,47 However, the relative contribution of secretory versus basal progenitor cell populations to epithelial maintenance and regeneration following injury remains controversial. Studies by Evans and colleagues 12 involving injury targeted to ciliated cells indicated that nonciliated secretory cells represent the preferred progenitor cell type of the bronchial epithelium.…”

mentioning

confidence: 99%

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

Hong

Reynolds

Watkins

et al. 2004

The American Journal of Pathology

479

390

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Commitment of the pulmonary epithelium to bronchial and bronchiolar airway lineages occurs during the transition from pseudoglandular to cannalicular phases of lung development, suggesting that regional differences exist with respect to the identity of stem and progenitor cells that contribute to epithelial maintenance in adulthood. We previously defined a critical role for Clara cell secretory protein-expressing (CE) cells in renewal of bronchiolar airway epithelium following injury. Even though CE cells are also the principal progenitor for maintenance of the bronchial airway epithelium, CE cell injury is resolved through a mechanism involving recruitment of a second progenitor cell population that we now identify as a GSI-B 4 reactive, cytokeratin-14-expressing basal cell. These cells exhibit multipotent differentiation capacity as assessed by analysis of cellular phenotype within clones of LacZ-tagged cells. Clones were derived from K14-expressing cells tagged in a cell-type-specific fashion by ligand-regulable Cre recombinase-mediated genomic rearrangement of the ROSA26 recombination substrate allele. We conclude that basal cells represent an alternative multipotent progenitor cell population of bronchial airways and that progenitor cell selection is dictated by the type of airway injury. Conducting airways of the lung are lined by a highly specialized epithelium whose composition and function varies along the proximal to distal axis. Despite a growing appreciation of mechanisms contributing to branching morphogenesis and lineage specification in the developing lung it is still unclear how a complex epithelium such as that present in the conducting airway is established and maintained through adulthood. Studies in the developing rat lung indicate that lineage restriction occurs during the transition from the pseudoglandular to cannalicular phases of lung development. At this time cells of the proximal airway lose the ability to respond to mesenchymally derived signals capable of inducing distal airway differentiation.

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Number and Proliferation of Basal and Parabasal Cells in Normal Human Airway Epithelium

Cited by 239 publications

References 20 publications

Growth of putative progenitors of type II pneumocytes in culture of human cystic fibrosis alveoli

Growth of putative progenitors of type II pneumocytes in culture of human cystic fibrosis alveoli

Superoxide Dismutase Inactivation in Pathophysiology of Asthmatic Airway Remodeling and Reactivity

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

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