Lead perturbs the regulation of spontaneous release of tissue plasminogen activator and plasminogen activator inhibitor-1 from vascular smooth muscle cells and fibroblasts in culture.
To evaluate the toxicity of lead on the blood fibrinolytic system during hemostasis, human aortic smooth muscle cells and human fetal lung fibroblasts were cultured in the presence of lead chloride. Tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) released were determined by enzyme immunoassay. It was found that lead decreased the release of both t-PA:Ag and PAI-1:Ag from vascular smooth muscle cells. On the other hand, in fibroblasts, the release of t-PA:Ag was markedly decreased whereas that of PAI-1:Ag was markedly increased by the metal. Fibrin zymography showed that lead reduced the plasminogen activator activity in the conditioned medium of both cell types. However, lead did not cause a nonspecific cell damage and an alteration of protein synthesis when evaluated by lactate dehydrogenase leakage and [14C]leucine incorporation, respectively. Lead accumulated within either vascular smooth muscle cells or fibroblasts in a dose-dependent manner; intracellular accumulation of calcium could be increased by lead. However, the effects of lead on the release of t-PA:Ag and PAI-1:Ag were different from those of calcium ionophore A23187. It was therefore suggested that regulation of spontaneous release of fibrinolytic proteins from subendothelial cells is disturbed by lead through intracellular calcium-independent pathway.
Yamamoto
C
C
Department of Environmental Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Miyamoto
A
A
Sakamoto
M
M
Kaji
T
T
Kozuka
H
H
D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007854:Lead / Q000633:toxicity*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000187:drug effects* / Q000378:metabolism
D017077:Culture Media, Conditioned; D017395:Plasminogen Activator Inhibitor 1; D007854:Lead; D000001:Calcimycin; D010959:Tissue Plasminogen Activator