Airway Inflammation after Controlled Exposure to Diesel Exhaust Particulates

Abstract

Epidemiologic evidence suggests a link between morbidity and mortality and levels of particulate matter in the atmosphere. We studied the inflammatory response to inhalation of diesel exhaust particulates (DEP) in normal volunteers. DEP were collected from the exhaust of a stationary diesel engine and were resuspended in an exposure chamber. Ten nonsmoking healthy volunteers were exposed for 2 h at rest to a controlled concentration of DEP (monitored at 200 microg/m(3) particulate matter of less than 10 microm aerodynamic diameter [PM(10)]) or air in a double-blind, randomized, crossover study. Exposures were followed by serial spirometry and measurement of pulse, blood pressure, exhaled carbon monoxide (CO), and methacholine reactivity, as well as sputum induction and venesection for up to 4 h after exposure, and a repeat of all these procedures at 24 h after exposure. There were no changes in cardiovascular parameters or lung function following exposure to DEP. Levels of exhaled CO were increased ater exposure to DEP, and were maximal at 1 h (air: 2.9 +/- 0.2 ppm [mean +/- SEM]; DEP: 4.4 +/- 0.3 ppm; p < 0.001). There was an increase in sputum neutrophils and myeloperoxidase (MPO) at 4 h after DEP exposure as compared with 4 h after air exposure (neutrophils: 41 +/- 4% versus 32 +/- 4%; MPO: 151 ng/ml versus 115 ng/ml, p < 0.01), but no change in concentrations of inflammatory markers in peripheral blood. Exposure to DEPs at high ambient concentrations leads to an airway inflammatory response in normal volunteers.

Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage.

“…It is interesting, therefore, that in a study in which normal human volunteers were exposed to DEPs, CO levels in the expired air was a more sensitive exposure marker than the presence of inflammatory products in the bronchoalveolar fluid (Nightingale et al 2000). This is in agreement with the exquisite sensitivity of the HO-1 promoter to oxidative stress in vivo and in vitro (Choi and Alam 1996;Nightingale et al 2000). HO-1 expression and CO generation are markers for airway inflammation in asthma (Horvath et al 1998).…”

“…In the process of heme catabolism, HO-1 also generates a gaseous substance, CO, which exerts anti-inflammatory effects in the lung and is exhaled in the expired air (Horvath et al 1998;Maines 1997). It is interesting, therefore, that in a study in which normal human volunteers were exposed to DEPs, CO levels in the expired air was a more sensitive exposure marker than the presence of inflammatory products in the bronchoalveolar fluid (Nightingale et al 2000). This is in agreement with the exquisite sensitivity of the HO-1 promoter to oxidative stress in vivo and in vitro (Choi and Alam 1996;Nightingale et al 2000).…”

Comparison of the Pro-Oxidative and Proinflammatory Effects of Organic Diesel Exhaust Particle Chemicals in Bronchial Epithelial Cells and Macrophages

“…Although some adverse effects may occur independently of oxidative stress, a stratified stress model implies that biological end points should be selected relevant to the level of oxidative stress and PM exposure. For instance, under the experimental conditions chosen by Nightingale et al (49), an increased CO level in the expired air was a more sensitive end point than the bronchoalveolar neutrophil content. This agrees with the idea that HO-1 is a more sensitive oxidative stress marker than IL-8 (Fig.…”

“…Not only does HO-1 constitute a very sensitive marker of oxidative stress, but its catalytic action on heme generates a potent antioxidant, bilirubin, as well as a gaseous substance, CO, that exert anti-inflammatory effects in the lung (48). Not surprising, therefore, the CO level in exhaled air is a sensitive in vivo marker for the proinflammatory effects of DEP in the lung (49). The molecular basis for initiating this antioxidant defense mechanism is the transcriptional activation of the HO-1 gene by a series of ARE in its promoter (11,47).…”

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

“…This study has provided most direct in vivo evidence that PM induce ROS generation and cause oxidative tissue damage. In humans, experimental DEP exposures result in increased CO in exhaled air; CO is the catalytic product of HO-1, which acts as a sensitive marker for PM-induced oxidative stress [69][70][71][72].…”