Impact of experimental peritonitis on bone marrow cell function

Abstract

Background: The effects of abdominal sepsis on the regulation of cell turnover in bone marrow and on the function of hematopoietic stem cells were investigated.

Methods: 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.

Results: 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.

Conclusions: 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.