Donaldson Ken, Brown David, Clouter Anna, Duffin Rodger, MacNee William, Renwick Louise, Tran Lang, Stone Vicki
The Biomedicine Research Group, School of Life Sciences, Napier University, 10 Colinton Road, Edinburgh EH10 5DT, Scotland, United Kingdom.
J Aerosol Med. 2002 Summer;15(2):213-20. doi: 10.1089/089426802320282338.
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.
超细颗粒是空气污染的一个组成部分，源自一次燃烧源，因此我们开展了一项关于超细颗粒所致肺损伤机制的研究计划。由低溶解度、低毒性材料制成的超细颗粒在大鼠肺中比由相同材料制成的可吸入细颗粒更具致炎作用。超细颗粒可通过独立于过渡金属释放的过程引发炎症，这一事实表明，超细炭黑的可溶性产物没有引发炎症的能力。驱动超细颗粒更强致炎作用的特性尚不清楚，但很可能与颗粒表面积有关，且涉及氧化应激。细胞内Ca(++)的增加可能是超细颗粒细胞效应的基础，尽管尚不清楚超细颗粒产生这种效应的机制。然而，与超细颗粒接触后，Ca(++)通过膜Ca(++)通道流入巨噬细胞的量增加，且涉及氧化应激。暴露于超细颗粒的巨噬细胞中Ca(++)增加可导致关键促炎基因如TNFα的转录。超细颗粒还可损害巨噬细胞吞噬和清除其他颗粒的能力，这可能具有促炎作用。
