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.

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