THE ACUTE-PHASE PROTEIN ALPHA-1-ANTITRYPSIN INHIBITS TRANSFERRIN UPTAKE IN PLC PRF/5 CELLS AND INCREASES RELEASE OF HEPATITIS-B VIRUS SURFACE-ANTIGEN AND ALPHA-FETOPROTEIN/

Background/aims The present study was designed to investigate whether the acute phase protein alpha-1-antitrypsin (alpha(1)-AT), which has a n inhibitory effect on transferrin (tf) receptor-mediated iron uptake in K562 and THP1 cells, has a similar effect in PLC/PRF/5 cells, This hepatic cell line is of specific interest because it is infected with hepatitis B virus (HBV). Therefore, we addressed the additional questi on whether alpha(1)-AT has any effect on cellular protein synthesis an d replication of HBV in PLC/PRF/5 cells. Methods Cells were incubated with various concentrations of alpha(1)-AT, dexamethasone, IL-6 and de sferrioxamine. HBs-AG, alpha-fetoprotein and albumin concentrations in culture media were measured using commercially available methods. For equilibrium inhibition binding experiments, cells were incubated with 85-182 pmol/l [I-125]tf. To study the potential effect of alpha(1)-AT on DNA synthesis we measured the incorporation of [H-3]thymidine into DNA. Results In equilibrium saturation binding experiments, [I-125]tf bound to PLC/PRF/5 cells with K-D 17.45 +/- 4.57 nM and a maximum den sity of binding sites of 267 285 +/- 39 915 sites/cell. In inhibition studies alpha(1)-AT demonstrated an apparently monophasic inhibition o f [I-125]tf to its receptor. At concentrations > 30 mu mol/l alpha(1)- AT inhibited the growth of PLC/PRF/5 cells up to approximately 50%. Th e inhibitory effect of alpha(1)-AT on DNA synthesis was not as potent as that on growth. At the highest concentration of 100 mu mol/l, alpha (1)-AT produced a 35% maximum inhibition of [H-3]thymidine incorporati on. Incubating PLC/PRF/5 cells with corticosteroids enhanced HBs-AG re lease significantly. Interestingly, alpha(1)-AT showed the same patter n of effects on cell metabolism and HBs-AG release as the corticostero ids. When we incubated the cells with 50 mu mol/l alpha(1)-AT, alpha-f etoprotein production increased significantly and HBs-AG release almos t doubled. Conclusion We have to assume that there is a specific mecha nism inducing HBs-AG release by alpha(1)-AT, as has been shown to be t he case with steroids. Eur J Gastroenterol Hepatol 10:497-502 (C) 1998 Lippincott-Raven Publishers.