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

Abstract

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.

Keywords:

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

Acknowledgments

The authors thank Shanie McCarty for outstanding animal care during the course of this experiment.

Author contributions

A.K.P. performed the study, and prepared the manuscript and preliminary figures; C-W.W. finalized the manuscript and all figures; X.Q. assisted in the study and data analysis; J.X. designed the original study; S.S-J. assisted in manuscript preparation and editing; D.U. oversaw the experimental exposures; D.Z. designed, guided and supported the experiments; K.E.P. oversaw the experimental design, final analysis and guidance in manuscript preparation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the National Institute of Occupational Safety and Health (NIOSH) U54 OH07750 and the National Institutes of Health (NIH) P51 OD011107. A.K.P. is supported by the National Institutes of Health (NIH) National Heart, Lung and Blood Institute (NHLBI) T32 HL007013.