Systemic Platelet Activation in Mice Exposed to Find Particulate Matter

摘要

We conducted five separate experiments designed to define the effects of ambient particles on the cardiovascular system. Mice were exposed to concentrated ambient particles (CAPs) less than 2.5 microns in diameter (PM2.5) or instilled with PM 2.5 from the Fresno, California area. Control animals were exposed to filtered air or physiological saline. Studies were conducted during summer and winter in both urban and rural areas. The three CAPS experiments were conducted in winter 2008, summer 2008, and winter 2009, and evaluated the effects of CAPs on the vascular and hemostatic systems. Later studies examined the effects of short term in vivo instillation of PM 2.5 that was collected during the CAPS experiments. In all studies, we determined the production of systemic inflammatory cytokines to evaluate the extent of pulmonary, coronary and systemic inflammation. Platelet upregulation and activation in response to agonist was evaluated by flow cytometry. We determined the expression and activation of key platelet integrins and the extent of alpha granule and lysosomal granule secretion. Complete blood counts were performed. Lung tissue was evaluated for changes in gene expression either by gene array or by laser capture micro-dissection. Particle exposed animals showed platelet activation in all studies compared to control animals, while proinflammatory cytokines were predominantly upregulated in the winter CAPs and winter instilled exposures. Exposure to winter particulate matter (PM) appears to activate different physiological outcomes than summer exposures.