Importance of components and sources in particle-induced lung inflammation: Role of PAHs and metals

Ambient particulate matter (PM) contribute to the development of adverse health effects in the lung and cardiovascular systems. PM has a complex composition and may contain a variety of different organic compounds and metals. We will investigate the possi ble role of PAHs and metals in PM-induced inflammation and cell death, and whether differences in biological activity between PM from different sources might be attributed to differences in PAH and metal content. In particular, it will be examined whether different metals and PAHs induce differential patterns of cytokine release. Selected metals and PAHs will be used to study the initial signalling mechanisms and pathways leading to cytokine synthesis and cell death in cell culture models. Furthermore, we will study how the balance between mechanisms involved in cell death, cell survival and inflammation may modulate the outcome of PAH and metal exposure. This may elucidate whether cytokine production and cell death are triggered by similar particle prope rties but at different doses, or whether completely different particle-properties and signalling pathways may be responsible for the two outcomes. Possible cooperative effects between different metals and PAHs will be examined to better understand the tox icology of PMs. In parallel to study the components, we will examine the potential of different combustion particles (CPs) to trigger cellular responses, and in particular chemokines. We will include wood-burning particles produced at different conditions , different biodiesel CPs, diesel CPs produced in absence and presence of particle filters and extracts from selected CPs. Our intention is to identify component groups responsible for the observed effects of CP and sensitive endpoints for mechanistic stu dies. In a cooperating, parallel project, prof. Sandström, Univ. of Umeå will test the same CPs by exposure of human volunteers in inhalation chambers, which opens for comparison of in vitro and in vivo effects.