Mediatory role of stem cell derived cells in LPS-induced splenic CFUs accumulation.

Injection of bacterial lipopolysaccharides (LPS) in LPS-responsive mice produces a transient increase of CFUs in spleen and blood but not in bone marrow. The cellular aspects of the mechanism underlying this response of the hemopoietic system to LPS were investigated. Bone marrow cells from LPS-high responder mice (BMC-H) of the C3Heb/FeJ and C57BL/ScSn strains were transferred to lethally irradiated histocompatible LPS-low responder C3H/HeJ and C57BL/10/ScCr mice and vice versa. Six to ten weeks after reconstitution recipient mice were tested with LPS. Six days after injection of LPS, CFUs numbers in blood and spleen of low-responders reconstituted with BMC-H showed a 10-17 fold increase compared with PBS-injected controls. Lethally irradiated LPS high-responders reconstituted with low-responder bone marrow cells (BMC-L) still produced a small but significant increase of splenic and blood CFUs numbers. These results suggest that relatively radioresistant stem cell-derived cells play an important role in the generation of a stimulus inducing the splenic CFUs accumulation following LPS injection. The decrease of femoral CFUs numbers was less prominent in mice reconstituted with BMC-L than in those reconstituted with BMC-H. Thus expression of the LPS locus is evident in both medullary and extra-medullary sites.

Restoration of hemopoiesis by CFU-S from different backgrounds in the mouse.

Liver from 14 day-old fetuses, bone marrow, spleen, and blood from normal adult mice, and bone marrow, spleen, blood, and liver from adult endotoxin (ET)-treated mice were used for isogeneic hemopoietic restoration in lethally whole-body irradiated mice. The number of CFU-S required to prevent 50% mortality of irradiated mice was about 3 for fetal liver, 7-10 for bone marrow, 20 for normal blood and for blood, liver, and spleen of ET-treated mice, and 80 for spleen of normal mice. CFU-S growth curves in femoral bone marrow and spleen showed some variations but the differences in survival of irradiated and protected mice could not easily be explained by differences in CFU-S growth curves. It can be concluded that the CFU-S from peripheral blood, although somewhat less effective than CFU-S from bone marrow, can be a valuable source of CFU-S for bone marrow transplantation.

Effects of serum complement levels on the mobilization of mature white blood cells in relation to mobilization of CFUS.

It was investigated whether the complement dependency of CFUS mobilization observed for certain mobilizing agents is unique for the CFUS compartment, or whether this mobilization reflects a more general mechanism, which involves also the mobilization of mature leukocytes. The number of all recognizable nucleated cell types in the blood was determined following the injection of the mobilizing agents, i.e. endotoxin, zymosan, cobra venom factor, proteinase, trypsin, dextran sulphate and the copolymer of polymethacrylic acid and styrene. The results indicate that if a mobilizing effect of a CFUS mobilizing agent on other nucleated cells occurs, this mobilization of nucleated cells is similarly inhibited or not by C3 to C9 depletion as is observed for the CFUS mobilization. The degree of inhibition is also comparable to the inhibition of CFUS mobilization. The significance of the complement system for the mobilization process is discussed.

Studies on the mechanism of haemopoietic stem cell (CFUs) mobilization. A role of the complement system.

A variety of substances can mobilize haemopoietic stem cells (CFUs) into the peripheral blood. In this study the involvement of the complement system in the mobilization process was investigated. Pretreatment of mice with the complement-activating factor of cobra venom (CoF), which lowered the serum C3 levels to 10-25% of the normal value, could completely prevent CFUs mobilization induced by high doses of CoF, endotoxin (ET) from Salmonella typhosa, inulin, zymosan and the proteolytic enzymes proteinase and trypsin. On the other hand, mobilization induced by the polyanions dextran sulphate and the copolymer of polymethacrylic acid and styrene could not be prevented, or at least affected only slightly. There appears to be a relationship between the extent of decomplementation by CoF and the extent of CFUs mobilization induced by ET. The results indicate that certain agents mobilize CFUs via the complement system, whereas other agents induce CFUs mobilization independent of the availability of complement components.