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

다국어 초록 (Multilingual Abstract)

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 Pb²? whereas the effects of Pb⁴?, another major form of Pb on erythrocytes are poorly understood yet. In this study, we investigated and compared the effects of Pb⁴?, Pb²? 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 Pb⁴?. Freshly isolated erythrocytes from human were incubated with Pb⁴?, Pb²?, Cd²? and Ag? and the exposure of phosphatidylserine (PS), key marker for procoagulant activation was measured using flow cytometry. As a result, while Cd²? and Ag? did not affect PS exposure, Pb⁴? and Pb²? induced significantly PS exposure in a dose-dependent manner. Of a particular note, Pb⁴? induced PS exposure with a similar potency with Pb²?. PS bearing microvesicle (MV), another important contributor to procoagulant activation was also generated by Pb⁴?. These PS exposure and MV generation by Pb⁴? were well in line with the shape change of erythrocyte from normal discocytes to MV shedding echinocytes following Pb⁴? treatment. Meanwhile, nonspecific hemolysis was not observed suggesting the specificity of Pb⁴?-induced PS exposure and MV generation. These results indicated that Pb⁴? could induce procoagulant activation of erythrocytes through PS exposure and MV generation, suggesting that Pb⁴? exposure might ultimately lead to increased thrombotic events.

목차 (Table of Contents)

• INTRODUCTION
• MATERIALS AND METHODS
• RESULTS
• DISCUSSION
• ACKNOWLEDGMENTS
• REFERENCES