Effect of sepsis after burn injury on the dynamics of granulopoiesis in mice

Rational strategies for the treatment of burn injury and infection require an improved understanding of the mechanisms by which immune suppression and pro-inflammatory signals interact. Here we study the dynamics of granulopoiesis in the bone marrow (BM) using a mouse burn/infection model to identify the roles that apoptosis, differentiation, proliferation and release play in the etiology of the immunologic response to burns and superimposed infection. We demonstrate that there is a rapid loss of mature granulocytes (CD11b⁺ Ly6G⁺) from the marrow during a primarily septic injury using a clinical isolate of Pseudomonas aeruginosa (PA-14). Due to the short timescale involved massive and specific release of granulocytes from the marrow is the most likely mechanism for the observed dynamics. There is also clear evidence of a drop in the bone marrow cellularity for animals with superimposed burn and sepsis. Using a simple population balance approach we demonstrate that a decreased cell residence time in the mature bone marrow pool could explain the observed rapid decline in its size.