Induction of Erythroid Colony Forming Cells (CFU-E) in Murine Spleen by Endotoxin

Abstract

The plasma clot culture system containing erythropoietin (Ep) permits erythroid precursors from bone marrow or spleen to form in vitro small colonies of hemoglobin-synthesizing erythroblasts (1). Early erythroid precursors (committed erythroid stem cells) most likely comprise a multistage compartment that is interposed between the pluripotential stem cells (CFU) and the morphologically recognizable proerythroblasts (2, 3). The position of the colony-forming erythroid precursors (CFU-E) within this compartment and the factors regulating or influencing their population size are not exactly known. Erythropoietin injection into hypertransfused mice has been shown by Gregory et al. (4) to increase the number of femoral or splenic CFU-E, but increasing the concentration of Ep in the medium above a plateau level failed to increase colony formation. The injection of endotoxin into mice is known to increase their splenic erythropoiesis as measured by 59Fe incorporation ( 5 , 6), and the present study was undertaken to examine the effect of endotoxin on the number of splenic CFU-E in the presence or absence of Ep. It will be shown that endotoxin injection indeed induced splenic CFU-E in normal mice and in mice whose endogenous erythropoietin production was suppressed by posthypoxic polycythemia. Differences in increases in CFU-E between those induced by Ep and those induced by endotoxin will be discussed.Methods. Female CF, mice of from 23 to 27 g body weight were used in groups of eight. Mice were made polycythemic by 3 weeks of exposure (18 hr/day) to an atmospheric pressure of from 380 to 340 mm Hg. Endotoxin (lipopolysaccharide B, S . typhosa, Difco) was diluted in normal saline and injected ip. Human erythropoietin (56 This study was supported by USPHS Grant AM 07239.

Effects of thrombopoietin and erythropoietin on platelet production in rebound‐thrombocytotic and normal mice

“…The results of these experiments indicate that Et contamination of Ep may have caused the depression of platelet production in mice. Endotoxin has been shown t o trigger stem cell proliferation [19], to depress marrow erythropoiesis and at the same time to stimulate RBC production in the spleen [20,21], t o depress the synthesis of Ep [22], and to inhibit the effects of exogenous Ep [22]. The present study shows that Et inhibited platelet production in mice in It is possible that Ep preparations used in the present work contained TSF.…”

Further Characterization of the Effect of Bacterial Lipopolysaccharide Preparations on Cyclic GMP Levels: The Importance of Macromolecular Synthesis

“…Second, both the concentration of these stem cells within the fetal liver and the cGMP response to LPS decline with increasing gestational age (1, 2, 13). Third, LPS increases splenic hematopoiesis when injected into mice ( 15,16) and elevates cGMP levels when added to cultures of rat adult spleen cells (3). Thus, it seems possible that the increase of cGMP levels produced by LPS is occurring in hematopoietic stem cells and may even be related to growth and differentiation of these cells.…”

Salmonella Infection Enhances Erythropoietin Production by the Kidney and Liver, Which Correlates with Elevated Bacterial Burdens

“…Furthermore, these erythroid alterations in the spleen are not a direct consequence of the type III secretion system encoded by SPI2 or bacterial expression of flagellin. Thus, erythroid dysregulation is induced in the spleen by virulent or highly attenuated Salmonella and is likely a direct consequence of host recognition of bacterial pathogen-associated molecular patterns (PAMPs) (35,36). In support of this idea, injection of mice with LPS alone also induced splenomegaly and extramedullary erythropoiesis.…”

“…Approximately 10 to 30% of the spleen of a healthy naive mouse is composed of erythroid cells, but this proportion rises to 80 to 85% at the peak of Salmonella-induced splenomegaly (33). This striking effect of Salmonella on erythroid development has been largely ignored despite the fact that several studies over the last 40 years have noted that bacterial endotoxin can affect erythropoiesis (35)(36)(37)(38).…”