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%
oxygen but increased apoptosis 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% but blunted at >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.