Burn injury-induced G-CSF secretion reduces spic+ erythroblastic island macrophages in the bone marrow and impairs medullary erythropoiesis.

Abstract

The erythroblastic island (EBI) functions as a niche in which erythroblastic island macrophages (EBIMφs) are positioned within rings of erythroblasts, providing support and signals that orchestrate efficient erythropoiesis. We postulated burn injury impacts the EBI niche, given the nearly universal presence of anemia and inflammation in burn patients, and a divergent myeloid transcriptional signature that we observed in murine bone marrow following burn injury, in which granulocyte colony-stimulating factor (G-CSF) secretion broadly attenuated the expression of EBIMφ marker genes. Notably, we identified the heme-induced transcription factor Spi-C as a robust marker of EBIMφs in Spicigfp/igfp mice. Two bone marrow cell populations, macrophages and Gr1-low monocytes, possessed cell-intrinsic Spic-GFP. Spic+ macrophages were distinguished by higher levels of green fluorescent protein, autofluorescence, F4/80, and CD163 while CD115 staining was negligible compared with Gr1-low monocytes. Application of Spicigfp/igfp mice in studies revealed a G-CSF-dependent reduction of Spic+ macrophages in postburn marrow, which coincided with a loss of erythroid cells and that G-CSF administration was sufficient to reduce Spic+ macrophages in the marrow. These results provide the first evidence that burn injuries impact the EBI niche through G-CSF-dependent reduction of Spic+ EBIMφs and support the use of Spicigfp/igfp mice in investigation of EBIMφs.