Heme regulates the development of iron-recycling macrophages from monocytes (sorted splenocytes)
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ABSTRACT: Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Further, cysteine-prol
ORGANISM(S): Mus musculus
SUBMITTER: MALAY HALDAR
PROVIDER: E-GEOD-46984 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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