Semester

Spring

Date of Graduation

2002

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Physiology, Pharmacology & Neuroscience

Committee Chair

Joseph K. H. Ma.

Abstract

Environmental exposure to diesel exhaust particles (DEP) has been of concern because of its potential contribution to the increased prevalence of acute and chronic airway diseases. The objective of this study was to investigate the role of thiol changes (due to DEP exposure) in immune responses. Rats were exposed to OVA, DEP, or both by intratracheal instillation (IT) and/or inhalation. IT-DEP exposure significantly increased the inflammatory parameters and thiol levels in both Sprague-Dawley and Brown Norway rats. Exposure to DEP and/or OVA resulted in significant increases in neutrophils, LDH, total protein, and albumin content in lavage fluid. Alveolar macrophage (AM) from DEP-exposed rats showed a time-dependent increase in intracellular cysteine (CYSH) and glutathione (GSH). In lymph node cells (LNC, the intracellular GSH increased significantly at 24 hours, and declined at 72 hours post exposure. LNC-CYSH, and AM-CYSH and -GSH were increased at both 24 and 72 hours. DEP acutely enhanced cystine uptake and reduction in both AM and LNC. In contrast, the intracellular level of GSH in DEP-exposed LNC was significantly reduced despite the increased CYSH level and GSH-ReductaseRTM activity when these cells were cultured with cystine. The DEP exposure stimulated GSH-R activity and resulted in increased conversion of cystine to CYSH in both cell types. Notable restoration of cystine uptake, reduction and GSH production was seen in AM of DEP-exposed OVA-challenged rats. Threshold effect on both CYSH and GSH levels in BAL and AM was seen after exposure to different concentrations of OVA alone. CB and DEP tended to increase lung IFN-gamma and IL-4 mRNA. The significant increases in serum OVA-specific IgG and IgE and the increase in IL-4 mRNA in lung tissue were consistent with an adjuvant effect of DEP or CB for OVA sensitization. In summary, DEP caused lung inflammation and thiol changes (in both AM and LNC and that these effects are particulate mediated.

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