Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: early mRNA induction by heme followed by iron-dependent protein expression

Constance Delaby , Nathalie Pilard , Hervé Puy , François Canonne-Hergaux , François Canonne-Hergaux (1)

1 ICSN - Institut de Chimie des Substances Naturelles

Tissue macrophages play an essential role in iron recycling through the phagocytosis of senescent erythrocytes. Following heme catabolism by heme oxygenase1 (HO1), they recycle iron back into the plasma through the iron exporter ferroportin (Fpn). We previously described a cellular model of erythrophagocytosis (EP), based on primary cultures of mouse bone-marrow derived macrophages (BMDM) and aged murine erythrocytes, and showed that EP induces changes in the expression profiles of Fpn and HO1. In the present paper, we demonstrate that heme derived from human or murine RBC or from an exogenous source of heme led to marked transcriptional activation of the Fpn and HO1 genes. Iron released from heme catabolism subsequently stimulated the Fpn mRNA and protein expression associated with localisation of the transporter at the cell surface, which probably promotes the export of iron into the plasma. These findings highlight a dual mechanism of Fpn regulation in BMDM, characterized by early induction of the gene transcription predominantly mediated by heme, followed by iron-mediated, post-transcriptional regulation of the exporter.

Mots clés: Life Sciences

Constance Delaby, Nathalie Pilard, Hervé Puy, François Canonne-Hergaux, François Canonne-Hergaux. Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages: early mRNA induction by heme followed by iron-dependent protein expression. Biochemical Journal, 2008, 411 (1), pp.123-131. ⟨10.1042/BJ20071474⟩. ⟨hal-00478904⟩