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Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Neonatal hyperoxic exposure persistently alters lung secretoglobins and annexin A1
Thomas M Raffay1, Morgan L Locy, Cynthia L Hill
1Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH 43205, USA.
Insights
Neonatal hyperoxia decreases Clara cell secretory protein (CCSP) in mice, altering lung immune responses. This suggests CCSP
Area of Science:
- Pulmonary Medicine
- Neonatal Research
- Immunology
Background:
- Bronchopulmonary dysplasia (BPD) in infants involves altered lung epithelial function.
- Decreased secretoglobins (SCGBs), including Clara cell secretory protein (CCSP), are observed in BPD.
- CCSP influences innate immune responses, as suggested by studies in CCSP knockout mice.
Purpose of the Study:
- To investigate if neonatal hyperoxia causes deficits in CCSP expression.
- To determine if these deficits are linked to persistent changes in lung SCGB and annexin A1 (ANXA1) expression.
- To explore the impact of hyperoxia-induced CCSP alterations on lung innate immune function.
Main Methods:
- Newborn C3H/HeN mice were exposed to room air or 85% oxygen.
- Mice were sacrificed at 14 days or recovered in room air for 14 days.
- Lung CCSP, SCGB3A1 protein/mRNA, ANXA1 charge characteristics, and macrophage numbers were analyzed.
Main Results:
- Neonatal hyperoxia followed by room air recovery decreased lung CCSP and SCGB3A1 protein, but not mRNA.
- Hyperoxia-induced alterations in ANXA1 charge persisted after room air recovery.
- These changes were associated with increased lung macrophage numbers.
Conclusions:
- Neonatal hyperoxia impairs CCSP expression, affecting lung SCGBs and ANXA1.
- Altered Clara cell function impacts lung innate immunity via immunomodulatory proteins.
- Further research is needed to elucidate CCSP's role in BPD pathogenesis.
Abstract:
Altered functions of the lung epithelial surface likely contribute to the respiratory morbidities in infants with bronchopulmonary dysplasia (BPD). Infants with BPD exhibit decreased expressions of secretoglobins (SCGBs), including Clara cell secretory protein (CCSP). Expression of lung SCGB and annexin A1 (ANXA1) is persistently altered in CCSP knockout mice suggesting that CCSP indirectly influences innate immune responses. The present studies tested the hypothesis that neonatal hyperoxic exposure induces deficits in CCSP expression that are associated with persistent alterations in lung SCGB and ANXA1 expression. Newborn C3H/HeN mice were exposed to room air (RA) or 85% O2 from birth and were sacrificed at 14 d or returned to RA for 14 d. Neonatal hyperoxia followed by RA recovery was associated with decreased lung CCSP and SCGB3A1 protein but not mRNA expression. Hyperoxia-induced alterations in the charge characteristics of ANXA1 were unchanged by RA recovery and were associated with elevated lung macrophage numbers. These findings support a model in which hyperoxia-induced alterations in Clara cell function influence lung innate immune function through effects on immunomodulatory proteins. Studies to determine the mechanism(s) by which CCSP alterations affect SCGBs, ANXA1, and innate immune responses in BPD are warranted.
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