Impact/Purpose:

Air pollution, including gases and particulate matter emitted from motor vehicles, has been associated with increases in both morbidity and mortality, but the underlying mechanisms responsible for these effects are not well understood. Insight into such mechanisms will aid in the understanding of human risk associated with air pollution.

Dr. Mark Witten and colleagues propose to investigate the inflammatory effects of diesel exhaust exposure on rat airways. The investigators will focus on the role of neurogenic inflammation, an inflammatory response defined by the release of neuropeptides, such as substance P (SP), from sensory nerve fibers known as C fibers located within the lung tissue. Neurogenic inflammation has been implicated in responses to inhaled irritants such as ozone and cigarette smoke and has been implied to play a role in asthma. The investigators hope that this study will provide valuable information on the pathogenic mechanisms involved in respiratory responses to diesel exhaust.

Description:

The investigators are among the first researchers to investigate neurogenic inflammation in the lungs of rats exposed to whole diesel exhaust. After exposure to both concentrations of diesel exhaust, consistently higher levels of plasma leakage and lower activity of the enzyme NEP were observed. Changes in levels of SP and its receptor NK1 were less consistent, however, and few changes were observed in cytokine levels. It is believed that the results will confirm previous findings of mild inflammatory responses after exposure to diesel exhaust.

Record Details:

Record Type:PROJECT( ABSTRACT )

Start Date:04/01/2000

Completion Date:03/31/2005

Record ID: 258842

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Related Organizations:

Role :OWNER

Organization Name :HEALTH EFFECTS INSTITUTE

Organization Name :HEI

Mailing Address :Charlestown Navy Yard, 120 Second Avenue

Citation :Boston

State :MA

Zip Code :2129



Role :OWNER

Organization Name :UNIVERSITY OF ARIZONA

Organization Name :HEI

Citation :Tucson

State :AZ

Zip Code :85721

Project Information:

Approach :

The investigators will expose female rats (8 weeks old) to two concentrations of whole diesel exhaust emissions (35 and 630 µg/m³ particulate matter) from a heavy-duty 1990s Cummins research engine. Exposures will be conducted over 3 weeks (4 hr/day, 5 days/week); neurogenic and other inflammatory markers were measured immediately after the end of exposure. Half of the rats in each exposure group will be pretreated with capsaicin, a neurotoxin that depletes sensory C fibers of neuropeptides and thereby inhibits the neurogenic inflammatory pathway. Control groups will be exposed to air. Cigarette smoke exposure (~400 µg/m³, 4 hr/day for 7 days) will provide a positive control. The investigators will then measure endpoints of neurogenic inflammation: SP protein and gene expression, density of the SP receptor neurokinin-1 (NK1), and activity of neutral endopeptidase (NEP), the enzyme that breaks down SP. They will also assess leakage of blood plasma into lung tissue and other inflammatory markers, such as levels of the cytokines interleukin (IL)-1ß, IL-6, IL-10, IL-12, and tumor necrosis factor α, numbers of inflammatory cells in lung tissue, and cellular lung pathology.

Investigators will collaborate with researchers from the University of Wisconsin to develop the diesel exhaust exposure system. Before animal exposures are started, they will evaluate a number of engine operation modes using the California Air Resources Board 8-mode test system for gaseous, particulate, and metal emissions. The investigators will use California Air Resources Board mode 6 for the animal experiments.

Cost :$.00

Research Component :Air Quality and Air Toxics

Approach :

The investigators will expose female rats (8 weeks old) to two concentrations of whole diesel exhaust emissions (35 and 630 µg/m³ particulate matter) from a heavy-duty 1990s Cummins research engine. Exposures will be conducted over 3 weeks (4 hr/day, 5 days/week); neurogenic and other inflammatory markers were measured immediately after the end of exposure. Half of the rats in each exposure group will be pretreated with capsaicin, a neurotoxin that depletes sensory C fibers of neuropeptides and thereby inhibits the neurogenic inflammatory pathway. Control groups will be exposed to air. Cigarette smoke exposure (~400 µg/m³, 4 hr/day for 7 days) will provide a positive control. The investigators will then measure endpoints of neurogenic inflammation: SP protein and gene expression, density of the SP receptor neurokinin-1 (NK1), and activity of neutral endopeptidase (NEP), the enzyme that breaks down SP. They will also assess leakage of blood plasma into lung tissue and other inflammatory markers, such as levels of the cytokines interleukin (IL)-1ß, IL-6, IL-10, IL-12, and tumor necrosis factor α, numbers of inflammatory cells in lung tissue, and cellular lung pathology.

Investigators will collaborate with researchers from the University of Wisconsin to develop the diesel exhaust exposure system. Before animal exposures are started, they will evaluate a number of engine operation modes using the California Air Resources Board 8-mode test system for gaseous, particulate, and metal emissions. The investigators will use California Air Resources Board mode 6 for the animal experiments.

Cost :$.00

Research Component :Health Effects