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Modulation of pulmonary inflammatory responses and anti-microbial defenses in mice exposed to diesel exhaust
Citation:
GOWDY, K., Q. T. KRANTZ, M. J. DANIELS, W. P. LINAK, I. JASPERS, AND M. I. GILMOUR. Modulation of pulmonary inflammatory responses and anti-microbial defenses in mice exposed to diesel exhaust. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 229(3):310-319, (2008).
Impact/Purpose:
DE composes a large part of the airborne particulate matter and has previously been shown by our lab and others to increase susceptibility to respiratory infections. This study was performed to examine early signaling in DE exposure that may affect the host defense mechanisms of the lung therefore making the pulmonary environment more permissive to infection. We did a comparative study of occupational levels using a state of the art inhalation facility to examine levels of relevant host defense molecules after acute diesel exhaust exposure.
Description:
Abstract: Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and antimicrobial defenses in an exposure model that had previously been shown to increase susceptibility to influenza. BALB/c mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m3 of diesel exhaust particles (DEP) for 4 hours per day for 1 or 5 days. One and 18 hours after one or five diesel exposures mice were euthanized to assess both immediate and delayed effects. DE exposure for 5 days at either concentration caused higher neutrophil numbers and lesion scoring compared to air controls. Intracellular adhesion molecule-1 (ICAM-1) which recruits inflammatory cells and is an entry site for rhinoviruses was increased immediately after 1 or 5 days of DE exposure. Several inflammatory and immune cytokines (TNF-α , MIP-2, IL-6, IFN-γ , and IL-13) were also upregulated at various timepoints and concentrations. In contrast, clara cell secretory protein (CCSP), surfactant protein A (SP-A), and surfactant protein D (SP-D) which are important host defense molecules, were significantly decreased at both the message and protein level with DE exposure. We conclude that exposure to moderate and high occupational levels of DE caused an increase in lung injury and inflammation, and a decrease in host defense molecules which could result in increased susceptibility to respiratory pathogens.
