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Exposure to diesel exhaust particles (DEP) alters the responsiveness of rats to bacterial lipopolysaccharide (LPS) insults.
Yang HM; Ma JYC; Castranova V; Barger MW; Ma JKH
Toxicologist 1998 Mar; 42(1-S):405
Exposure to DEP has been associated with increased susceptibility to pulmonary infection (Environ Res 37:44. 1985). Our hypothesis is that the functional activity of alveolar macrophages (AM) in response to bacterial LPS insults is diminished after DEP exposure. Male Sprague-Dawley rats (approximately 250 g) received a single intratracheal instillation of DEP (5 mg/kg) or saline, then were challenged intratracheally with LPS (10 mg/kg) or saline 3 days later. Rats were sacrificed 3 h after this second treatment and underwent bronchoalveolar lavage (BAL). BAL cell differentiation, protein and loctate dehydrogenase (LDH) in BAL fluidd were measured. Macrophage inftammatory protein 2 (MIP2, ELISA), tumor necrosis factor-alpha (TNF-a, ELISA) and nitric oxide (NO, Greiss assay) were monitored in both AM-conditioned supernatant and BAL fluid. Exposure to DEP resulted in increases in protein, LDH, neutrophil influx, lymphocyte influx and the production of MIP2. TNF-a and NO by AM. Exposure to LPS alone increased the infiltration of both neutrophils and lymphocytes and the production of MIP2. TNF-a and NO in AM supernatant and BAL fluid. Pretreatment of rats with DEP decreased the production of TNF-a. MIP2 and NO by AM in response 10 subsequent treatment with LPS below levels expected if the DEP and LPS responses were additive. In surnrnary, both DEP and LPS caused inflammation. However, preexposure to DEP decreased the secretory function of AM in response to subsequent LPS exposure, which may, in part, be responsible for the increased morbidity of infectious diseases after DEP exposure.
Diesel-exhausts; Diesel-emissions; Pulmonary-function; Pulmonary-disorders; Pulmonary-system-disorders; Animal-studies; Animals; Laboratory-animals; Laboratory-testing
The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington
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