Pulmonary responses of rats to intratracheal instillation of diesel exhaust particles: inflammation, oxidative stress and alveolar macrophage cytokine secretion.
Yang-HM; My-JYC; Castranova-V
Toxicologist 1997 Mar; 36(1)(Part 2):77
The objective of this study was to investigate the acute pulmonary responses of rats to diesel exhaust particles (DEP). Male Sprague-Dawley rats were dosed intratracheally with DEP (5 and 35 mg/kg body weight) or saline vehicle and killed 1, 3 and 7 days after the instillation. The pulmonary responses were evaluated by analysis of indicators of pulmonary inflammation, oxidative stress and injury in bronchoalveolar lavage (BAL) fluid, measurement of oxygen consumed by BAL cells, and analysis of the ability of alveolar macrophages (AM) to release interleukin-l (IL-I) and tumor necrosis factor-alpha (TNF-a). DEP instillation resulted in dose- and time-related pulmonary inflammation and injury, as evidenced by an increased infiltration of neutrophils and elevated levels of total proteins, albumin, lactate dehydrogenase and beta-galactosidase in BAL fluid. There were increased BAL cell oxygen consumption, phospholipidosis and elevated antioxidant enzyme activity observed in DEP-treated rats, indicating oxidative stress had occurred in these rats. DEP exposure resulted in transient secretion of TNF-a and persistent secretion of IL-1 by AM. The secretion of these cytokines by AM obtained from DEP-exposed rats following in vitro LPS stimulation was significantly depressed. In summary, DEP caused oxidative stress, that may be responsible for activating AM and leading to initiation and modulation of DEP-induced pulmonary inflammation and injury. IL-1 seems a more prominent contributor than TNF-a in this process. The suppression of the AM response to LPS after DEP exposure supports the concept that exposure to DEP may compromise the host defense system.
Toxic-dose; Toxic-materials; Toxins; Exposure-assessment; Exposure-levels; Exposure-limits; Alveolar-cells; Lung-tissue; Lung-disorders; Lung-cells; Respiratory-system-disorders; Pulmonary-system-disorders; Laboratory-animals; Animal-studies; Animals; Diesel-exhausts
The Toxicologist. Society of Toxicology 36th Annual Meeting, March 9-13, 2006, Cincinnati, Ohio