A COMPARISON OF THE SUPPRESSION OF HUMAN TRANSFERRIN SYNTHESIS BY LEAD AND LIPOPOLYSACCHARIDE

Transferrin, as the major iron-transport protein in serum and other bo dy fluids, has a central role in managing iron the body receives. Live r is a major site of transferrin synthesis, and in this study we prese nt evidence that liver synthesis of human transferrin is suppressed by both the toxic metal lead and bacterial lipopolysaccharide, an induce r of the hepatic acute phase response. The responses of intact endogen ous transferrin in the human hepatoma cell line HepG2 and chimeric hum an transferrin-chloramphenicol acetyltransferase genes in transgenic m ice were examined. In HepG2 cells, S-35-transferrin protein synthesis and mRNA levels were suppressed by 100 mu M and 10 mu M lead acetate a s early as 24 h after the initial treatment. Yet, synthesis of two pro teins known to respond in the hepatic acute phase reaction, complement C3 and albumin, was not altered by the lead treatment. In transgenic mouse liver, lead suppressed expression of chimeric human transferrin genes at both the protein and mRNA levels, but LPS only suppressed at the protein level. The study indicates that lead suppresses human tran sferrin synthesis by a mechanism that differs from the hepatic acute p hase response and that lead may also affect iron metabolism in humans by interfering with transferrin levels. (C) 1997 Elsevier Science Irel and Ltd.