Respiratory burst of neutrophils is not required for stem cell mobilization in mice

It has been suggested that mature neutrophils may play an essential role in the cascade of events leading to egress of stem cells from the bone marrow to the peripheral blood. To investigate further the role of mature neutrop hils and of reactive oxygen intermediates (ROIs), known to be involved in t he signal transduction of neutrophils, we used mice deficient in respirator y burst, and thus the production of ROIs, to study the involvement of this activation pathway in stem cell mobilization. B6 mice with chronic granulom atous disease (CGD) received either cyclophosphamide (200 mg/kg) on day 1 a nd granulocyte colony-stimulating factor (G-CSF) (250 mug/kg/d) on days 3-6 or a single dose of interleukin 8 (IL-8; 30 mug/mouse) as a mobilization r egimen. On day 7, the number of stem and progenitor cells in blood and bone marrow was compared with control B6 animals (with intact respiratory burst ). White blood cell counts, bone marrow cellularity and the frequency of gr anulocyte-macrophage colony-forming cells (GM-CFC), and cobblestone area-fo rming cells (CAFC) on days 7 (CAFC-7) and 28 (CAFC-28) were determined. Aft er cyclophosphamide and G-CSF (CY + G), both mouse strains showed considera ble mobilization of CAFC-7 and CFU-GM to the blood. Normal mice showed up t o a 1905-fold increase in progenitors per ml blood, whereas CGD mice showed up to a 264-fold increase in blood progenitors. IL-8 also induced mobiliza tion in both mouse strains. In addition to progenitors, primitive stem cell s measured as CAFC-28 and as CAFC at day 35 were also mobilized by both mob ilization protocols in normal as well as in CGD mice. In conclusion, respir atory burst and the subsequent signal transduction pathway do not appear to be required for mobilization of stem cells. Accordingly, neutrophils eithe r are not involved in stem cell mobilization or other signalling pathways w ithin neutrophils must exist that lead to the release of factors which acti vate stem cell egress from the bone marrow.