Impact of experimental peritonitis on bone marrow cell function.

Abstract

The effects of abdominal sepsis on the regulation of cell turnover in bone marrow and on the function of hematopoietic stem cells were investigated. In a new mouse model of abdominal sepsis (colon ascendens stent peritonitis [CASP]) the proliferation, apoptosis, and colony-forming capacity of bone marrow cells were determined. Both experimental peritonitis and sham surgery increased proliferation of bone marrow cells significantly (P < .01). Incubation with granulocyte-macrophage colony-stimulating factor but not granulocyte colony-stimulating factor further augmented proliferation of bone marrow cells from septic mice. In contrast to cell proliferation, bone marrow cell apoptosis was significantly (P < .001) increased in response to CASP but not to sham surgery. CASP surgery and treatment of normal bone marrow cells with lipopolysaccharide, tumor necrosis factor-alpha, interleukin 1 beta, and interferon gamma increased the number of apoptotic cells to a similar extent. Stem cell assays revealed that during the late phase of peritonitis the colony formation by granulocytic-monocytic precursors was increased, whereas mature erythroid colony-forming cells were suppressed. Incubation of normal bone marrow cells with lipopolysaccharide and cytokines showed similar effects. These results reveal differential effects of experimental peritonitis on various hematopoietic lineages and suggest a potential role of inflammatory mediators for the dysregulation of bone marrow cell function during abdominal sepsis.