Inhalation Of Concentrated Particulate Matter Produces Pulmonary Inflammation and Systemic Biological Effects in Compromised Rats

Abstract

Although significant progress has been made over the past few years, there is still debate on the causal fractions that are responsible for particulate matter (PM)-associated adverse health effects. A series of 1-d inhalation exposures to concentrated ambient particles (CAPs) were performed in compromised rats, focusing on pulmonary inflammation and changes in blood factors as biological outcomes. Studies were carried out in the Netherlands at an urban background location in Bilthoven, an industrialized location in the city of Utrecht, as well as at a location that is heavily dominated by freeway emissions. It was hypothesized that exposure to CAPs resulted in oxidative stress in the lung, producing a release of inflammatory mediators, which in turn can result in cardiovascular effects. Both spontaneously hypertensive rats and rats preexposed to ozone were studied. The effects were studied at 2d postexposure, focusing on pathology and cell proliferation, bronchoalveolar lavage fluid (BALF) analysis (including cytokines, biochemistry, cell differentials, cell viability and proliferation, and Clara-cell 16 protein), and blood analyses (fibrinogen, Clara-cell 16 protein, Von Willebrand factor, and cell differentials). Using CAPs exposures as a binary term, mild inflammation (increased numbers of neutrophils) and increased lung permeability (protein and albumin leakage in BALF) were evident. In addition, CAPs also produced increased fibrinogen concentrations in blood of spontaneously hypertensive rats. In conclusion, inhalation up to 3700 μg /m³ CAPs in the size range of 0.15–2.5 μm did induce statistically significant effects in the lung and blood, but the effects observed may not potentially be very biologically relevant. PM mass concentrations and lung permeability were weakly associated. This suggests that other PM metrics might be more appropriate.

This research was supported in part by funds from the National Institute for Public Health and the Environment, the Netherlands. The authors wish to thank Miriam Gerlofs for critically reviewing the manuscript of this article. The authors are grateful for the expert technical assistance of J. Bos, P. K. Beekhof, A. van de Kuil, F. M de Vlugt-van den Koedijk, J. P. Vermeulen, G. van Leuveren, J. Loendersloot, L. de la Fonteyne, and Y. Wallbrink-De Dreu.