The pulmonary toxicology of ultrafine particles.
Ultrafine particles are a component of air pollution, derived from primary combustion sources, and so we have undertaken a programme of study on the mechanisms of lung injury caused by ultrafine particles. Ultrafine particles made of low-solubility, low-toxicity materials are more inflammogenic in the rat lung than fine respirable, particles made from the same material. Ultrafine particles can cause inflammation via processes independent of the release of transition metals, as shown by the fact that soluble products from ultrafine carbon black have no ability to cause inflammation. The property that drives the greater inflammogenicity of ultrafines is unknown but very likely relates to particle surface area and involves oxidative stress. Increases in intracellular Ca(++) may underlie the cellular effects of ultrafines, although the mechanism whereby ultrafines have this effect is not understood. However, increased influx of Ca(++) into macrophages occurs via the membrane Ca(++) channels following contact with ultrafine particles, and involves oxidative stress. Increased Ca(++) in macrophages exposed to ultrafines can lead to the transcription of key pro-inflammatory genes such as TNFalpha. Ultrafine particles can also impair the ability of macrophages to phagocytose and clear other particles, and this may be pro-inflammogenic.
Donaldson
Ken
K
The Biomedicine Research Group, School of Life Sciences, Napier University, 10 Colinton Road, Edinburgh EH10 5DT, Scotland, United Kingdom. k.donaldson@napier.ac.uk
Brown
David
D
Clouter
Anna
A
Duffin
Rodger
R
MacNee
William
W
Renwick
Louise
L
Tran
Lang
L
Stone
Vicki
V
D000336:Aerosols / Q000633:toxicity; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002244:Carbon / Q000633:toxicity; D016207:Cytokines / Q000502:physiology; D007249:Inflammation / Q000209:etiology; D019570:Inhalation Exposure; D008168:Lung / Q000378:metabolism*; D008670:Metals / Q000633:toxicity; D010316:Particle Size; D010587:Phagocytosis / Q000502:physiology; D051381:Rats
D000336:Aerosols; D000393:Air Pollutants; D016207:Cytokines; D008670:Metals; D002244:Carbon