Effects of Paramyxoviral Infection on Airway Epithelial Cell Foxj1 Expression, Ciliogenesis, and Mucociliary Function

Look, Dwight C.; Walter, Michael; Williamson, Michael; Pang, Liyi; You, Yingjian; Sreshta, J. Nicholas; Johnson, Joyce E.; Zander, Dani S.; Brody, Steven L.

doi:10.1016/s0002-9440(10)63057-x

Cited by 88 publications

(97 citation statements)

References 46 publications

(90 reference statements)

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“…4, B and C). The abundance of ciliated cells mirrored the mouse trachea, but the number of CCSP-expressing cells was less than in vivo (18). After ALI day 14, ciliated cells covered about one-third of the apical cell surface [MTEC/NS, mean 30.9 Ϯ 8.6% (SD); MTEC/SF, mean 39.1 Ϯ 10.5% (SD)].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population

You

Richer

Huang

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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418

578

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Highly regulated programs for airway epithelial cell proliferation and differentiation during development and repair are often disrupted in disease. These processes have been studied in mouse models; however, it is difficult to isolate and identify epithelial cell-specific responses in vivo. To investigate these processes in vitro, we characterized a model for primary culture of mouse tracheal epithelial cells. Small numbers of cells seeded at low density (7.5 × 104 cells/cm2) rapidly proliferated and became polarized. Subsequently, supplemented media and air-liquid interface conditions resulted in development of highly differentiated epithelia composed of ciliated and nonciliated cells with gene expression characteristic of native airways. Genetically altered or injured mouse tracheal epithelial cells also reflected in vivo patterns of airway epithelial cell gene expression. Passage of cells resulted in continued proliferation but limited differentiation after the first passage, suggesting that transit-amplifying cell populations were present but with independent programs for proliferation and differentiation. This approach provides a high-fidelity in vitro model for evaluation of gene regulation and expression in mouse airway epithelial cells.

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Section: Resultsmentioning

confidence: 99%

“…Tracheas and membranes were prepared for scanning electron microscopy (EM), as previously described (18). Briefly, samples were fixed with 2.5% glutaraldehyde, stained with 1.25% osmium tetroxide, critical point dried under liquid carbon dioxide, gold sputter coated, and visualized on a Hitachi S-450 microscope (Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population

You

Richer

Huang

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

418

578

View full text Add to dashboard Cite

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“…The death rates of infected target cells were estimated to be between 2.1 and 13.5 day Ϫ1 , higher than our estimate of 1.2 day Ϫ1 . The difference in the epithelial cell death rates could be due to the relatively high virus production value assigned in our study, which was chosen based on direct measurements from in vitro systems using cultured airway epithelial cells (6,27,57). Based on these estimates, we fixed virus production at 100 EID 50 ⅐ ml Ϫ1 ⅐ cell Ϫ1 ⅐ day Ϫ1 and estimated innate virus clearance (c V ) as 4.2 day Ϫ1 .…”

Section: Discussionmentioning

confidence: 99%

Quantifying the Early Immune Response and Adaptive Immune Response Kinetics in Mice Infected with Influenza A Virus

Miao

Hollenbaugh

Zand

et al. 2010

J Virol

200

350

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Seasonal and pandemic influenza A virus (IAV) continues to be a public health threat. However, we lack a detailed and quantitative understanding of the immune response kinetics to IAV infection and which biological parameters most strongly influence infection outcomes. To address these issues, we use modeling approaches combined with experimental data to quantitatively investigate the innate and adaptive immune responses to primary IAV infection. Mathematical models were developed to describe the dynamic interactions between target (epithelial) cells, influenza virus, cytotoxic T lymphocytes (CTLs), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large data set obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (before day 5), the estimated half-life of infected epithelial cells is ϳ1.2 days, and the half-life of free infectious IAV is ϳ4 h. During the adaptive immune response (after day 5), the average half-life of infected epithelial cells is ϳ0.5 days, and the average half-life of free infectious virus is ϳ1.8 min. During the adaptive phase, model fitting confirms that CD8 ؉ CTLs are crucial for limiting infected cells, while virus-specific IgM regulates free IAV levels. This may imply that CD4 T cells and class-switched IgG antibodies are more relevant for generating IAV-specific memory and preventing future infection via a more rapid secondary immune response. Also, simulation studies were performed to understand the relative contributions of biological parameters to IAV clearance. This study provides a basis to better understand and predict influenza virus immunity.

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“…For example, in paramyxoviral infection of the mouse airway epithelium there is a loss and subsequent recovery of cilia. This loss and recovery of cilia are accompanied by a decrease and subsequent increase in Foxj1 with recovery from infection (Look et al, 2001). Elucidating the mechanisms regulating basal body anchoring to the apical cytoskeleton may thus have important implications with respect to understanding pulmonary epithelial diseases and may suggest novel therapeutic approaches to them.…”

Section: Discussionmentioning

confidence: 99%

Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells

Gomperts

Gong-Cooper

Hackett

2004

Journal of Cell Science

123

102

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The forkhead box transcription factor Foxj1 is required for cilia formation and left-right axis determination. To define the role of Foxj1 in ciliogenesis, microarray analysis was performed to identify differentially expressed genes in the pulmonary epithelium of foxj1 +/+ and foxj1 -/-mice. In the absence of Foxj1, the expression of calpastatin, an inhibitor of the protease calpain, decreased. RNase protection confirmed the decrease in calpastatin expression and decreased calpastatin was detected in the proximal pulmonary epithelium of foxj1 -/-mice by immunohistochemistry. No change was detected in the expression of calpain 2 in the pulmonary epithelium by western blot or immunohistochemistry. By western blot and immunofluorescence, ezrin, a substrate for calpain, was also found to decrease in the pulmonary epithelium of foxj1 -/-mice. No change in ezrin gene expression was found by RT-PCR. A decrease in ezrin binding phosphoprotein-50 (EBP-50) was also detected by immunofluorescence in the foxj1 -/-mouse pulmonary epithelium. Immunoelectron microscopy demonstrated ezrin associated with the basal bodies of cilia in the pulmonary epithelium. Treatment of tracheal explants from foxj1 -/-mice with a calpain inhibitor resulted in a partial reappearance of cilia observed in these mice. Additionally, following treatment of foxj1 -/-tracheal explants with calpain inhibitor, basal bodies were observed in an apical location along with relocalization of ezrin and EBP-50. Regulation of calpain activity by calpastatin thus provides a mechanism for regulating the anchoring of basal bodies to the apical cytoskeleton in ciliated cells. In the absence of Foxj1, decreased calpastatin expression with decreased ezrin and EBP-50 results in an inability of basal bodies to anchor to the apical cytoskeleton and subsequent failure of axonemal formation.

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Effects of Paramyxoviral Infection on Airway Epithelial Cell Foxj1 Expression, Ciliogenesis, and Mucociliary Function

Cited by 88 publications

References 46 publications

Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population

Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population

Quantifying the Early Immune Response and Adaptive Immune Response Kinetics in Mice Infected with Influenza A Virus

Foxj1 regulates basal body anchoring to the cytoskeleton of ciliated pulmonary epithelial cells

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