Opposing Effects of 60% Oxygen and Neutrophil Influx on Alveologenesis in the Neonatal Rat

Man, Yi; Jankov, Robert P.; Belcastro, Rosetta; Humes, Daryl; Copland, Ian B.; Shek, Samuel; Sweezey, Neil; Post, Martin; Albertine, Kurt H.; Auten, Richard L.; Tanswell, A. Keith

doi:10.1164/rccm.200402-215oc

Cited by 112 publications

(142 citation statements)

References 44 publications

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“…Control experiments confirmed that hyperoxia did not stimulate expression of the mT/mG reporter ( Figure E2) and that it did not activate excision of mT red in the absence of doxycycline. To confirm that the expansion of type II cells was not related to their morbidity, the study was repeated with 60% oxygen, which is still sufficient to disrupt lung development (20,33). Similar to the effects seen with 100% oxygen, EGFP was readily detected in alveolar cells of mice exposed to 60% oxygen ( Figures 5B and 5C).…”

Section: Neonatal Hyperoxia Stimulates Expansion Of Type II Cellsmentioning

confidence: 72%

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Yee¹,

Buczynski

O’Reilly³

2014

Am J Respir Cell Mol Biol

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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.

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Section: Neonatal Hyperoxia Stimulates Expansion Of Type II Cellsmentioning

confidence: 72%

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Yee¹,

Buczynski

O’Reilly³

2014

Am J Respir Cell Mol Biol

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“…First, increased expression of CXCR2 was observed in hyperoxic lungs [120]. Following exposure to 80% O 2 for 6 days, CXCR2 −/− mice showed reduced neutrophil sequestration, which is associated with significantly decreased lung vascular permeability, edema and injury [121].…”

Section: Proinflammatory Responses In Hyperoxic Lung Injurymentioning

confidence: 98%

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

Zaher

Miller

Morrow

et al. 2007

Free Radical Biology and Medicine

122

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Mechanical ventilation with hyperoxia is necessary to treat critically ill patients. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), which can cause acute inflammatory lung injury. One of the major effects of hyperoxia is the injury and death of pulmonary epithelium, which is accompanied by increased levels of pulmonary proinflammatory cytokines and excessive leukocyte infiltration. A thorough understanding of the signaling pathways leading to pulmonary epithelial cell injury/death may provide some insights into the pathogenesis of hyperoxia-induced acute inflammatory lung injury. This review focuses on epithelial responses to hyperoxia and some of the major factors regulating pathways to epithelial cell injury/death, and proinflammatory responses upon exposure to hyperoxia. We discuss in detail some of the most interesting players, such as, NF-κB, that can modulate both proinflammatory responses and cell injury/death of lung epithelial cells. A better appreciation for the functions of these factors will no doubt help us to delineate the pathways to hyperoxic cell death and proinflammatory responses.

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“…This strategy suppressed pulmonary inflammation and enhanced lung growth. 23 Pro-and anti-inflammatory cytokines Besides IL-8, other proinflammatory cytokines such as TNF-a, IL-1 and interleukin-6 (IL-6) are important mediators in the early inflammatory response. These cytokines are synthesized by alveolar macrophages, fibroblasts, type II pneumocytes and endothelial cells upon stimulation by hypoxia, hyperoxia, endotoxin, other bacterial cell wall constituents, and biophysical factors.…”

Section: Inflammatory Cells Endothelial Interactions and Chemotaxismentioning

confidence: 99%

Pulmonary inflammation and bronchopulmonary dysplasia

Speer

2006

J Perinatol

131

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Various pre-and postnatal risk factors, which act additively or synergistically induce an injurious inflammatory response in the airways and the pulmonary interstitium of preterm infants with bronchopulmonary dysplasia. This inflammatory response is characterized by an accumulation of neutrophils and macrophages as well as an arsenal of proinflammatory mediators that affect the endothelium and alveolar-capillary integrity. Besides proinflammatory cytokines and toxic oxygen radicals, lipid mediators as well as potent proteases may be responsible for acute lung injury. There is increasing evidence that an imbalance between pro-and anti-inflammatory factors, which should protect the alveoli and lung tissue, are key features in the pathogenesis of bronchopulmonary dysplasia. In addition, a subnormal generation of growth factors may affect alveolarization and vascular development in preterm infants with bronchopulmonary dysplasia. In this condensed review article, the current concepts on the possible role of inflammation in the evolution of bronchopulmonary dysplasia will be summarized.

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Opposing Effects of 60% Oxygen and Neutrophil Influx on Alveologenesis in the Neonatal Rat

Cited by 112 publications

References 44 publications

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

Pulmonary inflammation and bronchopulmonary dysplasia

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