Text

theses

Ozone is a ubiquitous urban air pollutant known to damage the lung. Injury is a result of both direct interaction of ozone and its oxidative products with proteins and lipids in the epithelial lining fluid of the lung and the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and inflammatory mediators by infiltrating inflammatory cells. Surfactant protein-D (SP-D) is a pulmonary collectin that down-regulates macrophage activation. In these studies we analyzed the effects of progressive pulmonary macrophage inflammation and emphysema associated with aging in mice lacking SP-D on the persistence of ozone-induced injury, macrophage activation, and altered functioning of the lung. We hypothesized that loss of SP-D results in increased sensitivity to ozone. Young (8 wk), middle age (27 wk), and elderly (80 wk) wild type (WT) and SPD-/- mice were exposed to air or ozone (0.8 ppm, 3 h). Bronchoalveolar lavage fluid (BAL) and tissue were collected 72 h later. Loss of SP-D resulted in increased sensitivity to inhaled ozone at 8 wk and 27 wk of age as observed by increased BAL protein, nitrogen oxides and chemotactic activity. Increased numbers of enlarged, vacuolated macrophages were also present. Aging was associated with increased macrophage numbers, alveolar wall rupture and increases in BAL protein, as well as Type II hyperplasia and expression of proliferating cell nuclear antigen. Heme oxygenase-1+ macrophages together with classically (iNOS+) and alternatively (mannose receptor+, YM-1+, or galectin-3+) activated macrophages also increased in aging SP-D-/- mice. In contrast, while increases in MR+, Ym1+, and galectin-3+ macrophages were observed in WT mice following ozone exposure, no changes were observed in SP-D-/- mice. In both WT and SP-D-/- mice, aging was associated with reduced lung stiffness. Ozone exposure caused alterations in tissue mechanics in WT mice, and both airway and tissue mechanics in SP-D-/- mice. Loss of SP-D led to increased sensitivity to ozone up to 27 wk of age, however at 80 wk, this was overwhelmed by the larger effects of age-related increases in baseline inflammation and lung injury. Understanding how these responses are regulated could improve disease prognosis in those exposed to air pollutants. 

ETD_4649

Ph.D.

Includes bibliographical references

Includes vita

by Angela M. Groves

http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000068867

doi:10.7282/T3HH6HPC

ETD doctoral

The author owns the copyright to this work.