Maea expressed by macrophages, but not erythroblasts, maintains postnatal murine bone marrow erythroblastic islands.

Abstract:

:The erythroblastic island (EI), formed by a central macrophage and developing erythroblasts (EBs), was first described decades ago and was recently shown to play an in vivo role in homeostatic and pathological erythropoiesis. The exact molecular mechanisms, however, mediating the interactions between macrophages and EBs remain unclear. Macrophage-EB attacher (Maea) has previously been suggested to mediate homophilic adhesion bounds bridging macrophages and EBs. Maea-deficient mice die perinatally with anemia and defective erythrocyte enucleation, suggesting a critical role in fetal erythropoiesis. Here, we generated conditional knockout mouse models of Maea to assess its cellular and postnatal contributions. Deletion of Maea in macrophages using Csf1r-Cre or CD169-Cre caused severe reductions of bone marrow (BM) macrophages, EBs, and in vivo island formation, whereas its deletion in the erythroid lineage using Epor-Cre had no such phenotype, suggesting a dominant role of Maea in the macrophage for BM erythropoiesis. Interestingly, Maea deletion in spleen macrophages did not alter their numbers or functions. Postnatal Maea deletion using Mx1-Cre or function inhibition using a novel monoclonal antibody also impaired BM erythropoiesis. These results indicate that Maea contributes to adult BM erythropoiesis by regulating the maintenance of macrophages and their interaction with EBs via an as-yet-unidentified EB receptor.

journal_name

Blood

journal_title

Blood

authors

Wei Q,Boulais PE,Zhang D,Pinho S,Tanaka M,Frenette PS

doi

10.1182/blood-2018-11-888180

subject

Has Abstract

pub_date

2019-03-14 00:00:00

pages

1222-1232

issue

11

eissn

0006-4971

issn

1528-0020

pii

blood-2018-11-888180

journal_volume

133

pub_type

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