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 produc tion are now the accepted hallmarks of systemic inflammatory response syndr ome, no information is available on the status of bone marrow monocyte prod uction under injury conditions; neither has the balance between the two arm s 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 nuclea ted and monocyte progenitor enriched bone marrow cells. Dual color flow cyt ometry was used to document the distribution pattern of monocyte progenitor s. Macrophage colony-stimulating factor receptor density in monocyte progen itors was assessed by I-125 macrophage colony-stimulating factor binding as say. Results Burn sepsis induced circulating monocytosis and granulocytopenia. Colony-fo rming assays demonstrated an increase in the growth potential of monocyte p rogenitors 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 macroph age colony-stimulating factor receptor expression in monocyte progenitors i n burn sepsis. Conclusions The data validate the premise that enhanced monocytopoiesis in thermal inju ry and sepsis results from an imbalance in myelopoiesis that is driven by t he increased expression of macrophage colony-stimulating factor receptor.