Inhibitory effect of lead on the release of tissue plasminogen activator from human vascular endothelial cells in culture.
To evaluate the toxicity of lead on the blood fibrinolytic system, vascular endothelial cells from human umbilical vein were cultured in the presence of lead and the content of tissue plasminogen activator antigen (t-PA:Ag) released into the medium was determined by enzyme immunoassay. It was found that lead significantly decreased the t-PA:Ag release from the cells. Although heavy metals including cadmium, mercury, cobalt, manganese, nickel, zinc and copper as well as lead each had an inhibitory effect, lead was the potent inhibitor. Lead significantly disturbed thrombin up-regulation of t-PA:Ag release and significantly amplified endothelin-1 down-regulation of it. Incorporation of [3H]thymidine into the acid-insoluble fraction of the cell layer was significantly increased by lead; however, that of [14C]leucine was unchanged by the metal. In lead-treated cells, a significant accumulation of lead was observed but calcium content was increased slightly. From these results, it was suggested that lead decreased the release of t-PA:Ag from cultured endothelial cells without nonspecific inhibition of protein synthesis; lead may stimulate the calcium-dependent down-regulation of endothelial cell t-PA:Ag release by calcium or by mimicking calcium.
Kaji
T
T
Department of Environmental Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Yamamoto
C
C
Sakamoto
M
M
Kozuka
H
H
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000633:toxicity*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*
D007854:Lead; D010959:Tissue Plasminogen Activator; D002118:Calcium