THE HEAVY-METAL LEAD MODULATES THE EXPRESSION OF BOTH TNF-ALPHA AND TNF-ALPHA RECEPTORS IN LIPOPOLYSACCHARIDE-ACTIVATED HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

It has been shown that lead (Ph) potentiates lipopolysaccharide (LPS) lethality in animals by increasing the secretion and uptake or reactiv ity of tumor necrosis factor-alpha (TNF-alpha). Herein we report that PbCl2 increased TNF-alpha secretion from LPS-treated human peripheral blood mononuclear cells (PBMC) in a concentration- and time-dependent manner, PbCl2 also increased total cellular TNF-Cl levels but had no e ffect on the steady-state levels of TNF-alpha mRNA. PbCl2 decreased me mbrane-associated TNF-alpha (mTNF-alpha) on LPS-treated monocytes, whe reas PbCI2 increased TNF-alpha receptor (TNF-R) p55 surface expression , and had no effect on TNF-Rp75 surface expression by LPS-treated mono cytes. Overall, the results suggest that PbCl2 increased TNF-alpha exp ression by posttranscriptional mechanisms in human PBMC, and enhances the reactivity and uptake of TNF-alpha by increasing the surface expre ssion of TNF-R P55.