Oxygen dose responsiveness of human fetal airway smooth muscle cells

Maintenance of blood oxygen saturation dictates supplemental oxygen administration to premature infants, but hyperoxia predisposes survivors to respiratory diseases such as asthma. Although much research has focused on oxygen effects on alveoli in the setting of bronchopulmonary dysplasia, the mecha...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2012-10, Vol.303 (8), p.L711-L719
Main Authors: Hartman, William R, Smelter, Dan F, Sathish, Venkatachalem, Karass, Michael, Kim, Sunchin, Aravamudan, Bharathi, Thompson, Michael A, Amrani, Yassine, Pandya, Hitesh C, Martin, Richard J, Prakash, Y S, Pabelick, Christina M
Format: Article
Language:English
Subjects:
Adult
Airway management
Apoptosis
Asthma
Asthma - epidemiology
Asthma - metabolism
Asthma - pathology
Calcium - metabolism
Cell Proliferation
Cells, Cultured
Fetus - cytology
Fibroblasts - drug effects
Fibroblasts - metabolism
Fibroblasts - pathology
Gene expression
Humans
Hyperoxia
Hyperoxia - epidemiology
Hyperoxia - metabolism
Hyperoxia - pathology
Hypoxia - epidemiology
Hypoxia - metabolism
Hypoxia - pathology
Infant, Newborn
Infant, Premature
Mitochondria - metabolism
Myocytes, Smooth Muscle - cytology
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - metabolism
Oxygen
Oxygen - administration & dosage
Oxygen - adverse effects
Pulmonary Alveoli - drug effects
Pulmonary Alveoli - metabolism
Pulmonary Alveoli - pathology
Risk Factors
Trachea - cytology
Trachea - embryology
Trachea - metabolism
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Summary:Maintenance of blood oxygen saturation dictates supplemental oxygen administration to premature infants, but hyperoxia predisposes survivors to respiratory diseases such as asthma. Although much research has focused on oxygen effects on alveoli in the setting of bronchopulmonary dysplasia, the mechanisms by which oxygen affects airway structure or function relevant to asthma are still under investigation. We used isolated human fetal airway smooth muscle (fASM) cells from 18-20 postconceptual age lungs (canalicular stage) to examine oxygen effects on intracellular Ca(2+) ([Ca(2+)](i)) and cellular proliferation. fASM cells expressed substantial smooth muscle actin and myosin and several Ca(2+) regulatory proteins but not fibroblast or epithelial markers, profiles qualitatively comparable to adult human ASM. Fluorescence Ca(2+) imaging showed robust [Ca(2+)](i) responses to 1 μM acetylcholine (ACh) and 10 μM histamine (albeit smaller and slower than adult ASM), partly sensitive to zero extracellular Ca(2+). Compared with adult, fASM showed greater baseline proliferation. Based on this validation, we assessed fASM responses to 10% hypoxia through 90% hyperoxia and found enhanced proliferation at 60%, effects accompanied by appropriate changes in proliferative vs. apoptotic markers and enhanced mitochondrial fission at >60% oxygen. [Ca(2+)](i) responses to ACh were enhanced for 60% oxygen. These results suggest that hyperoxia has dose-dependent effects on structure and function of developing ASM, which could have consequences for airway diseases of childhood. Thus detrimental effects on ASM should be an additional consideration in assessing risks of supplemental oxygen in prematurity.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00037.2012