Increased monocyte actin polymerization in rat blood after intratracheal instillation of air pollution particles.

BACKGROUND: Exposure to particulate air pollution is associated with an increased risk of cardiovascular disease. The mechanism by which exposure increases risk is poorly understood but could involve changes in the flow properties of blood. OBJECTIVE: The aim of this investigation was to assess the effect, in rats, of intratracheal instillation of particulate air pollution on leukocyte flow properties by measurement of polymorphonucleocyte (PMN) and monocyte actin polymerisation. METHODS: Rats were exposed to particulate air pollution by intratracheal instillation of PM10. Blood was collected from test and control animals at 3 days (n=10) and 6 weeks (n=10) after dust instillation. Partial differential leukocyte counts were performed. The intracellular F-actin content of blood PMNs and monocytes was determined by staining with FITC-phalloidin and flow cytometric determination of mean florescence intensity (MFI). RESULTS: There were no significant changes in PMN MFI (p=0.369, ANOVA) or cell counts (p=0.753, ANOVA). There was a significant increase in monocyte MFI (p=0.004, ANOVA) and a decrease in monocyte cell count (p=0.003, ANOVA) in instilled rats. CONCLUSIONS: Intratracheal instillation of air pollution particles resulted in an increase in blood monocyte actin polymerisation, which may cause trapping of monocytes. This could be a mechanism by which exposure to air pollution increases the risk of cardiovascular disease.

Inflammation, edema, and peripheral blood changes in lung-compromised rats after instillation with combustion-derived and manufactured nanoparticles.

Increased exposure to pollution has been implicated in cardiovascular malfunction, and although studies show a relationship between PM10 and mortality, the exact biological causes are unclear. This study investigated how compromised lungs respond to instillation of nanoparticles, and the links between exposure to nanoparticles and the subsequent effects on the blood. Instillation of diesel exhaust particles and Cabosil caused significant permeability and inflammatory changes in both bleomycin-treated and control lungs, as shown by increased lung surface protein and lung:body weight ratio. This was true in edematous and maximally repairing lungs, but without significant hematological alterations. Plasma viscosity, a renowned marker for cardiovascular disease, correlated strongly statistically with free cell numbers, type I cell marker rT140, and lung acellular protein. These correlations are a new and novel insight into the mechanisms linking air pollution to cardiovascular mortality.

The PPAR-gamma activator, Rosiglitazone, inhibits actin polymerisation in monocytes: involvement of Akt and intracellular calcium.

Monocyte hyperactivation as seen in diabetes results in increased cytoskeletal rigidity and reduced cell deformability leading to microchannel occlusions and microvascular complications. The thiazolidinediones (TZDs) are PPAR-gamma agonists that have been reported to exert beneficial non-metabolic effects on the vasculature. This study demonstrates that the TZD, Rosiglitazone, significantly reduces f-MLP-induced actin polymerisation in human monocytic cells (p < 0.05). Two of the key signalling processes known to be involved in the regulation of cytoskeletal remodelling were investigated: PI(3)K-dependent Akt phosphorylation and intracellular calcium concentration [Ca(2+)](i). The PI(3)K inhibitor, Wortmannin, ameliorated f-MLP-induced actin polymerisation (p < 0.05), while the Ca(2+) sequestration inhibitor, thapsigargin, induced actin depolymerisation (p < 0.05), confirming the involvement of both processes in cytoskeletal remodelling. Rosiglitazone significantly reduced f-MLP activation of Akt (p < 0.05), and significantly increased [Ca(2+)](i) in both resting and f-MLP-stimulated cells (p < 0.05). Therefore, Rosiglitazone interacts with signalling events downstream of occupancy of the f-MLP receptor, to modulate cytoskeletal remodelling in a PPAR-gamma-independent manner. To our knowledge, these results are the first to present evidence that a PPAR-gamma agonist can modulate actin remodelling in monocytes, and may therefore be protective against microvascular damage in diabetes.