These results will serve to adjust the composition of the laboratory generated PM for the controlled clinical, animal and in vitro studies. The inclusion of this group in a consortia arrangement allows access to a large-scale ongoing European study evaluating ultrafine particle effects. Monitoring of the autonomic function of the heart will investigate how these changes in the inflammatory state relate to alterations in autonomic control. The result of this Core will be a valuable input for the clinical, animal and in vitro studies with respect to planned mixed PM-oxidant exposures. Emigration of inflammatory cells from blood to tissue sites involves up-regulation of adhesion molecules and other markers on vascular endothelium and on circulating leukocytes.
Platelets become activated and adhere to endothelium and leukocytes.
Endothelial activation may further contribute to the increase in exhaled NO concentrations seen with airway inflammation. Possible adverse cardiac events in patients with critical coronary lesions, as a consequence of increased blood coagulability, platelet activation, and endothelial dysfunction. The animal studies are designed to be complementary to the field and controlled clinical studies and to form a link to the mechanistic in vitro studies. Our mechanistic hypothesis is that inhaled ultrafine particles activate resident inflammatory cells leading to oxidative stress and production of cytokines, and that this primary response is further amplified through inflammatory cell recruitment and elaboration of both inflammatory and epithelial cell-derived cytokines. Based upon our preliminary data we further hypothesize that the primary response is greater to UP than AP, and which is further enhanced by endotoxin exposure.