Neonatal Hyperoxia Increases Sensitivity of Adult Mice to Bleomycin-Induced Lung Fibrosis

Yee, Min; Buczynski, Bradley W.; Lawrence, B. Paige; O’Reilly, Michael A.

doi:10.1165/rcmb.2012-0238oc

Cited by 22 publications

(20 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increase in total AEC2 cells following exposure to hyperoxia was recently reported by Yee et al (34). In this study, we observed that ActRIIB-Fc treatment reduced the percentage of proliferating cells while keeping the percentage of proliferating AEC2 cells unchanged.…”

Section: Articlessupporting

confidence: 84%

Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice

et al. 2015

View full text Add to dashboard Cite

show abstract

Section: Articlessupporting

confidence: 84%

Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Interestingly, the enhanced inflammation associated with certain viral infections has recently been recognized as a potential exacerbating agent in the development of lung fibrosis (42). Moreover, we have recently shown that neonatal hyperoxia increases the sensitivity of adult mice to bleomycin-induced lung fibrosis, which was primarily associated with a disproportionate increase in neutrophils, which is not observed in mice infected with influenza A virus (49). Depletion of neutrophils in these mice with anti-Gr-1 antibody reduced the early activation of transforming growth factor-␤1 and attenuated the hyperoxia-enhanced fibrosis.…”

Section: Discussionmentioning

confidence: 93%

Neonatal hyperoxia alters the host response to influenza A virus infection in adult mice through multiple pathways

Buczynski

Yee

Martin

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

Exposing preterm infants or newborn mice to high concentrations of oxygen disrupts lung development and alters the response to respiratory viral infections later in life. Superoxide dismutase (SOD) has been separately shown to mitigate hyperoxia-mediated changes in lung development and attenuate virus-mediated lung inflammation. However, its potential to protect adult mice exposed to hyperoxia as neonates against viral infection is not known. Here, transgenic mice overexpressing extracellular (EC)-SOD in alveolar type II epithelial cells are used to test whether SOD can alleviate the deviant pulmonary response to influenza virus infection in adult mice exposed to hyperoxia as neonates. Fibrotic lung disease, observed following infection in wild-type (WT) mice exposed to hyperoxia as neonates, was prevented by overexpression of EC-SOD. However, leukocyte recruitment remained excessive, and levels of monocyte chemoattractant protein (MCP)-1 remained modestly elevated following infection in EC-SOD Tg mice exposed to hyperoxia as neonates. Because MCP-1 is often associated with pulmonary inflammation and fibrosis, the host response to infection was concurrently evaluated in adult Mcp-1 WT and Mcp-1 knockout mice exposed to neonatal hyperoxia. In contrast to EC-SOD, excessive leukocyte recruitment, but not lung fibrosis, was dependent upon MCP-1. Our findings demonstrate that neonatal hyperoxia alters the inflammatory and fibrotic responses to influenza A virus infection through different pathways. Therefore, these data suggest that multiple therapeutic strategies may be needed to provide complete protection against diseases attributed to prematurity and early life exposure to oxygen.

show abstract

“…Because type II cells are selectively lost in human emphysema (35), their loss may contribute to the alveolar simplification seen in adult mice exposed to hyperoxia as neonates (20). Type II cells also express innate immune genes (36) and act as progenitor cells after injury (37), which may explain why the mice are also sensitive to influenza A virus infection and bleomycin-induced lung fibrosis (23,38,39). Hence, persistent pulmonary diseases attributed to prematurity, and more specifically early life exposure to oxygen, may be related to overexpansion of type II cells at birth that are depleted over time.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Yee¹,

Buczynski

O’Reilly³

2014

Am J Respir Cell Mol Biol

Self Cite

View full text Add to dashboard Cite

Supplemental oxygen used to treat infants born prematurely disrupts angiogenesis and is a risk factor for persistent pulmonary disease later in life. Although it is unclear how neonatal oxygen affects development of the respiratory epithelium, alveolar simplification and depletion of type II cells has been observed in adult mice exposed to hyperoxia between postnatal Days 0 and 4. Because hyperoxia inhibits cell proliferation, we hypothesized that it depleted the adult lung of type II cells by inhibiting their proliferation at birth. Newborn mice were exposed to room air (RA) or hyperoxia, and the oxygenexposed mice were recovered in RA. Hyperoxia stimulated mRNA expressed by type II (Sftpc, Abca3) and type I (T1a, Aquaporin 5) cells and inhibited Pecam expressed by endothelial cells. 5-Bromo-2'-deoxyuridine labeling and fate mapping with enhanced green fluorescence protein controlled statically by the Sftpc promoter or conditionally by the Scgb1a1 promoter revealed increased Sftpc and Abca3 mRNA seen on Day 4 reflected an increase in expansion of type II cells shortly after birth. When mice were returned to RA, this expanded population of type II cells was slowly depleted until few were detected by 8 weeks. These findings reveal that hyperoxia stimulates alveolar epithelial cell expansion when it disrupts angiogenesis. The loss of type II cells during recovery in RA may contribute to persistent pulmonary diseases such as those reported in children born preterm who were exposed to supplemental oxygen.

show abstract

Neonatal Hyperoxia Increases Sensitivity of Adult Mice to Bleomycin-Induced Lung Fibrosis

Cited by 22 publications

References 52 publications

Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice

Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice

Neonatal hyperoxia alters the host response to influenza A virus infection in adult mice through multiple pathways

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Contact Info

Product

Resources

About