Effect of Lead(IV) Acetate on Procoagulant Activity in Human Red Blood Cells.

Lead (Pb) is a ubiquitously occurring environmental heavy metal which is widely used in industry and human life. Possibly due to a global industrial expansion, recent studies have revealed the prevalent human exposure to Pb and increased risk of Pb toxicity. Once ingested by human, 95% of absorbed Pb is accumulated into erythrocytes and erythrocytes are known to be a prime target for Pb toxicity. Most of the studies were however, focused on Pb whereas the effects of Pb, another major form of Pb on erythrocytes are poorly understood yet. In this study, we investigated and compared the effects of Pb, Pb and other heavy metals on procoagulant activation of erythrocytes, an important factor for the participation of erythrocytes in thrombotic events in an effort to address the cardiovascular toxicity of Pb. Freshly isolated erythrocytes from human were incubated with Pb, Pb, Cd and Ag and the exposure of phosphatidylserine (PS), key marker for procoagulant activation was measured using flow cytometry. As a result, while Cd and Ag did not affect PS exposure, Pb and Pb induced significantly PS exposure in a dose-dependent manner. Of a particular note, Pb induced PS exposure with a similar potency with Pb. PS bearing microvesicle (MV), another important contributor to procoagulant activation was also generated by Pb. These PS exposure and MV generation by Pb were well in line with the shape change of erythrocyte from normal discocytes to MV shedding echinocytes following Pb treatment. Meanwhile, nonspecific hemolysis was not observed suggesting the specificity of Pb-induced PS exposure and MV generation. These results indicated that Pb could induce procoagulant activation of erythrocytes through PS exposure and MV generation, suggesting that Pb exposure might ultimately lead to increased thrombotic events.