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

• Published in: Toxicological research (Seoul) 2009-12, Vol.25 (4), p.175-180
• Main Authors: Kim, Keun-Young, Lim, Kyung-Min, Shin, Jung-Hun, Noh, Ji-Yoon, Ahn, Jae-Bum, Lee, Da-Hye, Chung, Jin-Ho
• Format: Article
• Language: English
• Subjects: Biomedicine; Pharmacology/Toxicology
• ISSN: 1976-8257; 2234-2753
• DOI: 10.5487/TR.2009.25.4.175

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 2+ whereas the effects of Pb 4+ , another major form of Pb on erythrocytes are poorly understood yet. In this study, we investigated and compared the effects of Pb 4+ , Pb 2+ 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 4+ . Freshly isolated erythrocytes from human were incubated with Pb 4+ , Pb 2+ , Cd 2+ and Ag + and the exposure of phosphatidylserine (PS), key marker for procoagulant activation was measured using flow cytometry. As a result, while Cd 2+ and Ag + did not affect PS exposure, Pb 4+ and Pb 2+ induced significantly PS exposure in a dose-dependent manner. Of a particular note, Pb 4+ induced PS exposure with a similar potency with Pb 2+ . PS bearing microvesicle (MV), another important contributor to procoagulant activation was also generated by Pb 4+ . These PS exposure and MV generation by Pb 4+ were well in line with the shape change of erythrocyte from normal discocytes to MV shedding echinocytes following Pb 4+ treatment. Meanwhile, nonspecific hemolysis was not observed suggesting the specificity of Pb 4+ -induced PS exposure and MV generation. These results indicated that Pb 4+ could induce procoagulant activation of erythrocytes through PS exposure and MV generation, suggesting that Pb 4+ exposure might ultimately lead to increased thrombotic events.