Procoagulant changes in human macrophages induced by environmental microparticles [PM₁₀]: a possible pathogenetic mechanism in cardiovascular disease

Abstract number: P0956a

Morrison E. R., Gilmour P. S., Donaldson K., Macnee W., Vickers M. A., Ford I., Greaves M.

Universities of Aberdeen and Edinburgh, UK

In epidemiological studies a strong relationship has been confirmed between increasing concentrations of environmental particles [PM₁₀ and PM₂₅] and acute cardiovascular events including myocardial infarction and stroke. No plausible pathogenetic mechanism has been demonstrated to explain this association. Recently it has been demonstrated that inhaled particles pass into the systemic circulation in humans [1]. Therefore, we hypothesized that vascular events may be triggered by coagulation activation on cell surfaces induced by contact with environmental particles. Human peripheral blood monocyte-derived macrophages and a human bronchial epithelial cell line were exposed to PM₁₀ and supernatants examined for procoagulant activity in a plasma recalcification time assay. Control experiments employed culture medium only or H₂O₂. Both PM₁₀ and H₂O₂ induced release of procoagulant into culture supernatant from both cell types [shortening of clotting time vs. control with PM₁₀ 31% with macrophages and 19% with epithelial cells, mean of three experiments, P < 0.001 and <0.01, respectively]. In order to characterize the procoagulant activity from macrophages induced by PM₁₀ we went on to determine the effects of these particles on surface expression of negatively charged phospholipid by annexin V binding, and tissue factor mRNA expression by RT-PCR. Finally we measured macrophage interleukin 8 mRNA expression and release in response to PM₁₀. Environmental particles induced macrophage tissue factor mRNA expression and significantly increased bound annexin V. Furthermore IL8 message and release were significantly enhanced also. We have demonstrated, for the first time, that environmental particles associated with increased cardiovascular risk can activate macrophages in vitro with transformation to a procoagulant phenotype which may be mediated through apoptosis/negatively charged phospholipid exposure and tissue factor expression. This may represent a novel prothrombotic mechanism triggered when environmental particles reach the systemic circulation.

1  Nemmar, , et al.Circulation, 2002, 105: 411–4.