Differential lung inflammation and injury with tobacco smoke exposure in Wistar Kyoto and spontaneously hypertensive rats

Alexa K. Pham, Ching Wen Wu, Xing Qiu, Jingyi Xu, Suzette Smiley-Jewell, Dale Uyeminami, Priya Upadhyay, Dewei Zhao, Kent E. Pinkerton

Research output: Contribution to journalArticlepeer-review


Objective: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and has been associated with periods of intense lung inflammation. The objective of this study was to characterize whether similar rat strains, possessing different genetic predispositions, might play a role in exacerbating the pathophysiology of COPD-like cellular and structural changes with progressive 12-week exposure to tobacco smoke (TS). Normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats were compared. Materials and methods: WKY and SH rats were exposed to filtered air or to tobacco smoke at a particulate concentration of 80 mg/m3 for 4, 8, or 12 weeks. Necropsy was performed 24 h after the last exposure to obtain cells by bronchoalveolar lavage for total cell and differential counts. Scoring of lung tissues and immunohistochemical staining for M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages were performed on paraffin-embedded lung sections. Results and discussion: With progressive exposure, TS-exposed SH rats demonstrated significant airspace enlargement, mucin production, and lung inflammation compared to their FA control and TS-matched WKY rats. Moreover, SH rats also demonstrated increased expression of the M1 marker in alveolar macrophages compared to FA control, as well as the M2 marker compared to controls and TS-exposed WKY rats. Conclusion: The progressive tobacco smoke exposure contributes to persistent lung injury and inflammation that can be significantly enhanced by rat strain susceptibility in the genesis of COPD.

Original languageEnglish (US)
JournalInhalation toxicology
StateAccepted/In press - 2020


  • chronic obstructive pulmonary disease
  • macrophage
  • spontaneously hypertensive rats
  • Tobacco smoke
  • Wistar Kyoto rats

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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