Neonatal hyperoxia increases airway reactivity and inflammation in adult mice

Vasantha H.S. Kumar, Satyanarayana Lakshminrusimha, Sergei Kishkurno, Babu S. Paturi, Sylvia F. Gugino, Lori Nielsen, Huamei Wang, Rita M. Ryan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Supplemental O2 to treat bronchopulmonary dysplasia (BPD) in premature infants, is a major risk factor producing alteration in lung function, airway reactivity, and predisposition to respiratory infections. This study explores inflammatory and airway responses following neonatal hyperoxia in adult mice. Methods: Newborn mouse litters were randomized to 85% O2 or room air (RA) on P3 for 12 days; mice were sacrificed either on P15 or at 15 weeks following recovery in RA. Airway hyper reactivity (AHR) was assessed in vivo (8 and 12 weeks) and in vitro (15 weeks) with methacholine; Lung and BAL were assayed for inflammatory mediators, cell counts, CD3 immunohistochemistry, and histopathology. Results: Hyperoxic mice had increased airway reactivity at baseline and following methacholine challenge in vivo (8 and 12 weeks); isolated tracheal rings had a significantly higher constriction response to methacholine in vitro compared to RA group. Inflammatory markers were higher at 2 weeks (MCP-1, IL-12, INF-γ) and at 15 weeks (LTB4, VEGF); Lipoxin-A4 was lower in the hyperoxia group at both time points. Increased airway smooth muscle thickness and angiogenesis in the lung was seen at 15 weeks. Hyperoxic lungs exhibited alveolar simplification at 2 and 15 weeks. Absolute lymphocyte count was higher in lavage fluid with an increased CD3 cell count at 15 weeks suggesting persistent inflammation in adult mice following neonatal hyperoxia. Conclusions: Exposure to hyperoxia in newborn mice increases long-term airway reactivity with persistent lung inflammation associated with a marked increase in lymphocytes, suggesting long-term consequences in adults. Pediatr Pulmonol. 2016;51:1131–1141.

Original languageEnglish (US)
Pages (from-to)1131-1141
Number of pages11
JournalPediatric Pulmonology
Volume51
Issue number11
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Fingerprint

Hyperoxia
Inflammation
Methacholine Chloride
Lung
Air
Cell Count
Recovery Room
Dimercaprol
Bronchopulmonary Dysplasia
Leukotriene B4
Therapeutic Irrigation
Lymphocyte Count
Interleukin-12
Premature Infants
Constriction
Respiratory Tract Infections
Vascular Endothelial Growth Factor A
Smooth Muscle
Pneumonia
Immunohistochemistry

Keywords

  • airway reactivity
  • cytokines
  • hyperoxia
  • inflammation
  • lymphocytes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Kumar, V. H. S., Lakshminrusimha, S., Kishkurno, S., Paturi, B. S., Gugino, S. F., Nielsen, L., ... Ryan, R. M. (2016). Neonatal hyperoxia increases airway reactivity and inflammation in adult mice. Pediatric Pulmonology, 51(11), 1131-1141. https://doi.org/10.1002/ppul.23430

Neonatal hyperoxia increases airway reactivity and inflammation in adult mice. / Kumar, Vasantha H.S.; Lakshminrusimha, Satyanarayana; Kishkurno, Sergei; Paturi, Babu S.; Gugino, Sylvia F.; Nielsen, Lori; Wang, Huamei; Ryan, Rita M.

In: Pediatric Pulmonology, Vol. 51, No. 11, 01.11.2016, p. 1131-1141.

Research output: Contribution to journalArticle

Kumar, VHS, Lakshminrusimha, S, Kishkurno, S, Paturi, BS, Gugino, SF, Nielsen, L, Wang, H & Ryan, RM 2016, 'Neonatal hyperoxia increases airway reactivity and inflammation in adult mice', Pediatric Pulmonology, vol. 51, no. 11, pp. 1131-1141. https://doi.org/10.1002/ppul.23430
Kumar, Vasantha H.S. ; Lakshminrusimha, Satyanarayana ; Kishkurno, Sergei ; Paturi, Babu S. ; Gugino, Sylvia F. ; Nielsen, Lori ; Wang, Huamei ; Ryan, Rita M. / Neonatal hyperoxia increases airway reactivity and inflammation in adult mice. In: Pediatric Pulmonology. 2016 ; Vol. 51, No. 11. pp. 1131-1141.
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AB - Background: Supplemental O2 to treat bronchopulmonary dysplasia (BPD) in premature infants, is a major risk factor producing alteration in lung function, airway reactivity, and predisposition to respiratory infections. This study explores inflammatory and airway responses following neonatal hyperoxia in adult mice. Methods: Newborn mouse litters were randomized to 85% O2 or room air (RA) on P3 for 12 days; mice were sacrificed either on P15 or at 15 weeks following recovery in RA. Airway hyper reactivity (AHR) was assessed in vivo (8 and 12 weeks) and in vitro (15 weeks) with methacholine; Lung and BAL were assayed for inflammatory mediators, cell counts, CD3 immunohistochemistry, and histopathology. Results: Hyperoxic mice had increased airway reactivity at baseline and following methacholine challenge in vivo (8 and 12 weeks); isolated tracheal rings had a significantly higher constriction response to methacholine in vitro compared to RA group. Inflammatory markers were higher at 2 weeks (MCP-1, IL-12, INF-γ) and at 15 weeks (LTB4, VEGF); Lipoxin-A4 was lower in the hyperoxia group at both time points. Increased airway smooth muscle thickness and angiogenesis in the lung was seen at 15 weeks. Hyperoxic lungs exhibited alveolar simplification at 2 and 15 weeks. Absolute lymphocyte count was higher in lavage fluid with an increased CD3 cell count at 15 weeks suggesting persistent inflammation in adult mice following neonatal hyperoxia. Conclusions: Exposure to hyperoxia in newborn mice increases long-term airway reactivity with persistent lung inflammation associated with a marked increase in lymphocytes, suggesting long-term consequences in adults. Pediatr Pulmonol. 2016;51:1131–1141.

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