Differential regulation and expression of stress proteins and ferritin in human monocytes

We investigated the regulation and expression of ferritin in human cells by exposing peripheral blood monocytes (PBM) to heat shock (HS), opsonized sh eep red blood cells (RBC), and iron. Iron induced ferritin but had no effec t on stress protein expression. HS did not induce ferritin, indicating that ferritin is not a heat shock protein (HSP), at least in human PBM. In cont rast, erythrophagocytosis (EP), a model for oxidative stress and endogenous iron release, induced HSP, heme oxygenase (HO), and ferritin. During EP, t he antioxidant flavonoid quercetin prevented the induction of ferritin and HO, while it had no effect on the induction of ferritin by iron. In contras t, the iron chelator o-phenanthroline prevented the induction of ferritin d uring both EP and iron exposure. Differential effects of the transcriptiona l inhibitor actinomycin D on the various stress proteins revealed transcrip tional regulation of HSP and HO during EP, whereas the induction of ferriti n was posttranscriptionally regulated. We propose that while ferritin is no t an HSP, its induction during EP is mediated through the action of ROS and is promoted by the iron released from RBC. Induction of ferritin and the s ubsequent iron sequestration may protect PBM from oxidative injury by limit ing the iron-catalysed free radical reactions during EP. (C) 1999 Wiley-Lis s, Inc.