Ultrafine Particulate Matter Combined With Ozone Exacerbates Lung Injury in Mature Adult Rats With Cardiovascular Disease

Abstract

Particulate matter (PM) and ozone (O3) are dominant air pollutants that contribute to development and exacerbation of multiple cardiopulmonary diseases. Mature adults with cardiovascular disease (CVD) are particularly susceptible to air pollution-related cardiopulmonary morbidities and mortalities. The aim was to investigate the biologic potency of ultrafine particulate matter (UFPM) combined with O3 in the lungs of mature adult normotensive and spontaneously hypertensive (SH) Wistar-Kyoto rats. Conscious, mature adult male normal Wistar-Kyoto (NW) and SH rats were exposed to one of the following atmospheres: filtered air (FA); UFPM (∼ 250 μg/m3); O3 (1.0 ppm); or UFPM + O3 (∼ 250 μg/m3 + 1.0 ppm) combined for 6 h, followed by an 8 h FA recovery period. Lung sections were evaluated for lesions in the large airways, terminal bronchiolar/alveolar duct regions, alveolar parenchyma, and vasculature. NW and SH rats were similarly affected by the combined-pollutant exposure, displaying severe injury in both large and small airways. SH rats were particularly susceptible to O3 exposure, exhibiting increased injury scores in terminal bronchioles and epithelial degeneration in large airways. UFPM-exposure groups had minimal histologic changes. The chemical composition of UFPM was altered by the addition of O3, indicating that ozonolysis promoted compound degradation. O3 increased the biologic potency of UFPM, resulting in greater lung injury following exposure. Pathologic manifestations of CVD may confer susceptibility to air pollution by impairing normal lung defenses and responses to exposure.

Figure 1.

Terminal bronchioles and alveolar ducts from NW and SH rats by experimental exposure. Representative histological sections of (A) FA-exposed NW rat and (B) SH rat and (C) UFPM-exposed NW rat (D) and SH rat. (E) O₃-exposed NW rat and (F) SH rat. (G) UFPM + O₃-exposed NW rat and (H) SH rat. Sections were stained with hematoxylin and eosin, bar = 100 μm. Note: Arrowheads denote areas of injury and inflammation. Abbreviations: NW, normal Wistar rat; SH, spontaneously hypertensive rat; FA, filtered air; UFPM, ultrafine particulate matter; O₃, ozone; UFPM + O₃, ultrafine particulate matter combined with ozone; TB, terminal bronchiole; AV, alveolar duct.

Figure 2.

Bronchial epithelium of large intrapulmonary airways from NW and SH rats by experimental exposure. Representative histological sections of (A) FA-exposed NW rat and (B) SH rat and (C) UFPM-exposed NW rat and (D) SH rat. (E) O₃-exposed NW rat and (F) SH rat. (G) UFPM + O₃-exposed NW rat and (H) SH rat. Sections were stained with hematoxylin and eosin, bar = 50 μm. Arrowheads denote areas of injury and inflammation. Abbreviations: NW, normal Wistar rat; SH, spontaneously hypertensive rat; FA, filtered air; UFPM, ultrafine particulate matter; O₃, ozone; UFPM + O₃, ultrafine particulate matter combined with ozone; L, lumen.

Figure 3.

Increased lung injury in SH rats resulting from O₃ exposure. A, O₃ exposure resulted in increased TB epithelial necrosis (p = .002) in SH rats compared to NW rats. B, O₃ exposure-induced significant (p = .014) LA cilia cell loss/necrosis in SH rats, which was absent in NW rats. C, PMN leukocyte infiltration of the terminal bronchiole epithelium was significantly increased (p = .015) in O₃-exposed SH rats compared to O₃-exposed NW rats. D, O₃ exposure resulted in increased exudate (p = .008) in SH rats compared to NW rats. Abbreviations: NW, normal Wistar rat; SH, spontaneously hypertensive rat; O₃, ozone; TB, terminal bronchiole; LA, large airway; PMN, polymorphonuclear leukocyte; the Mann-Whitney test was used to calculate the difference between strains in response to each exposure. Values are shown as the means ± SEM by strain. *p < .05.