Myeloid commitment shifts toward monocytopoiesis after thermal injury and sepsis

Objective To demonstrate enhanced bone marrow monocytopoiesis in response to thermal injury and sepsis and to provide a mechanism for this observation. Summary Background Data Although monocyte activation and the resultant dysregulated cytokine production are now the accepted hallmarks of systemic inflammatory response syndrome, no information is available on the status of bone marrow monocyte production under injury conditions; neither has the balance between the two arms of myelopoiesis (monocytopoiesis and granulocytopoiesis) been delineated. Methods Peripheral blood absolute neutrophil and monocyte counts were determined 72 hours after the initial injury in sham, burn, and burn sepsis mice. Colony-forming potential in response to colony-stimulating factors (granulocyte, macrophage, and granulocyte/macrophage) was determined in both total nucleated and monocyte progenitor enriched bone marrow cells. Dual color flow cytometry was used to document the distribution pattern of monocyte progenitors. Macrophage colony-stimulating factor receptor density in monocyte progenitors was assessed by I-125 macrophage colony-stimulating factor binding assay. Results Burn sepsis induced circulating monocytosis and granulocytopenia. Colony-forming assays demonstrated an increase in the growth potential of monocyte progenitors and a significant decrease in granulocyte progenitors after burn and burn sepsis. Flow cytometric analysis of early (ER-MP12) and late (ER-MP20) monocyte progenitors showed an increase in monocyte lineage growth in burn sepsis. Radioligand binding assay demonstrated an increase in macrophage colony-stimulating factor receptor expression in monocyte progenitors in burn sepsis. Conclusions The data validate the premise that enhanced monocytopoiesis in thermal injury and sepsis results from an imbalance in myelopoiesis that is driven by the increased expression of macrophage colony-stimulating factor receptor.