The Effect of Bacterial Infection on Granulopoiesis 1

Abstract

Abstract

Colony-stimulating factor (CSF) is a well-established specific promoter of the committed stem cell colony-forming unit in culture (CFU-C) in vitro and thought to be a true regulator of granulopoiesis in vivo as well. However, the mechanisms involved in the regulation of granulopoiesis are still controversial. Bacterial products, like endotoxin and live bacteria, enhance levels of serum CSF in vitro and in vivo both in animals and in man. Data from our laboratory in germ-free mice showed evidence that high levels of bacteria stimulate production of granulocytes by activating the CSF-CFU-C system and that inhibition of granulocyte production may be simply due to clearance of bacteria by granulocytes. This study has been undertaken to determine the role of bacterial infection in conventional mice in the regulation of granulopoiesis in vivo. C57/bl 6J mice were injected intraperitoneally (ip) with 1 × 10⁴ Escherichia coli (E. coli). The animals were evaluated for the following parameters: serum CSF, bone marrow CFU-C, the absolute number of granulocytes in the peripheral blood, and the number of bacteria in peripheral blood and abdominal cavity. Groups of five mice were investigated at multiple time points after injection. The results show peak levels of bacteria both in peripheral blood and abdominal cavity at the 1-hr time point. There is a steady and marked rise in serum CSF reaching a first peak 8 hr, a second peak 96 hr after the injection. The number of CFU-C is increased at the 48- and the 120-hr time point. A pronounced rise in the absolute number of granulocytes is seen 2 hr after infection, which seems to be independent of the activation of stem cells. These findings demonstrate a temporal relationship between the peak in the number of bacteria, release of mature granulocytes, rise in serum CSF, and subsequent activation of bone marrow CFU-C. Following rises in CFU-C there are no marked elevations in peripheral blood granulocytes.