Details

Autor(en) / Beteiligte

• Noel, John G
• Ramser, Seth W
• Pitstick, Lori
• Bonamer, John P
• Mackenzie, Bryan
• Seu, Katie G
• Kalfa, Theodosia A
• Cancelas, Jose A
• Gardner, Jason C

Titel

M-CSF supports medullary erythropoiesis and erythroid iron demand following burn injury through its activity on homeostatic iron recycling

Ist Teil von

• Scientific reports, 2022-01, Vol.12 (1), p.1235-1235, Article 1235

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• M-CSF receptor signaling supports the development and survival of mononuclear phagocytes and is thought to play a role in post burn anemia by promoting myeloid lineage bias. We found M-CSF secretion was increased in burn patients and a murine model of post burn ACI, so we neutralized M-CSF in ACI mice to determine if erythropoiesis was improved. Instead, M-CSF blockade further impaired erythropoiesis and erythroid cells access to iron. M-CSF blockade enhanced inflammatory cytokine secretion, further increased systemic neutrophil counts, and led to tissue iron sequestration that was dependent, in part, on augmented IL-6 secretion which induced hepcidin. Deleterious effects of post burn M-CSF blockade were associated with arrest of an iron recycling gene expression signature in the liver and spleen that included Spi-C transcription factor and heme oxygenase-1, which promote heme metabolism and confer a non-inflammatory tone in macrophages. Hepatic induction of these factors in ACI mice was consistent with a recovery of ferroportin gene expression and reflected an M-CSF dependent expansion and differentiation of Spi-C+ monocytes into Kupffer cells. Together, this data indicates M-CSF secretion supports a homeostatic iron recycling program that plays a key role in the maintenance of erythroid cells access to iron following burn injury.