Role of the macrophage in erythropoiesis

Abstract

Macrophages, which are derived from precursor cells in the bone marrow, differentiate specifically under the influence of the local microenvironment. Resident macrophages in hematopoietic tissues can be distinguished from other stromal cells and monocytes by immunostaining with monoclonal antibody F4/80 and anti-Forssman glycosphingolipid antibody, respectively. Erythroid colony-forming units adhere to a resident macrophage and differentiate to erythroblasts in the presence of erythropoietin (EPO), resulting in the formation of an erythroblastic island. Resident macrophages play a supportive role in erythropoiesis, probably by preventing apoptosis of the erythroid precursors via adhesive interaction between very late activation antigen 4 and vascular cell adhesion molecule 1. Herein is proposed a model of erythropoiesis based on cooperative interaction between EPO and resident macrophages.

Hypoxic stress underlies defects in erythroblast islands in the Rb-null mouse

“…Nevertheless, it should be emphasized that cultures performed at atmospheric oxygen concentration (21%), as described in this paper, resulted in release of erythroblasts from macrophages earlier in terminal differentiation than reported in vivo. 2,32 Further studies will be required to examine the effect of hypoxia on erythroblast island integrity in vivo. However, our data predict that the expression and/or interaction of key adhesion molecules on the surfaces of the red cells and macrophages may be sensitive to oxygen tension.…”

“…[1][2][3] Proposed roles for macrophages in erythroid differentiation include a simple scaffolding function, 4 promotion of red cell proliferation, 5 provision of concentrated EPO, direct transfer of iron or iron-regulating factors, 6 inhibition of apoptosis, and more recently clear evidence has emerged testifying to the importance of macrophages in the engulfment of nuclei extruded by mature red cells. 7 Mice carrying a targeted deletion of the Rb tumor suppressor gene in their germ line die at E13.5 to E14.5 of gestation, exhibiting extensive cell death in multiple tissues, including the fetal liver, and this has been attributed to systemic ischemia due to defective placental function and anemia.…”

Ineffective erythropoiesis in Stat5a−/−5b−/− mice due to decreased survival of early erythroblasts

“…This may be due to more efficient clearance of apoptotic cells in adult spleen. 31 Significant levels of apoptosis were detected in neonatal spleens from Stat5a Ϫ/Ϫ 5b Ϫ/Ϫ mice (see below).…”

Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis

“…With the exception of regulation of infl ammation, studies documenting a direct role of MPs on cell behavior are scant and include intestinal progenitor proliferation (65), erythroblast proliferation and maturation (68), and oligodendrocytic diff erentiation and myelination (69). In vitro studies have shown that the MP activation state may direct neural progenitor diff erentiation toward either neurogenesis or oligodendrogenesis (70).…”