AM218, a new polyanionic polysaccharide, induces radioprotection in mice when administered shortly before irradiation.

We have shown that the polyanionic polysaccharide AM218 improves the survival rate of the potentially lethally irradiated mice. This radioprotective effect was highly dependent on the administration schedule, the most efficient protocol being that in which the drug was given shortly before irradiation. The haematopoietic implications in the pharmacological action of AM218 were confirmed by the improved recovery in the three peripheral blood lineages observed in the AM218-treated mice. However, because of a marked increase observed in the number of white blood cells during the period of highest mortality of the control irradiated mice, effects on the neutrophil lineage may account for the effects mediated by AM218 in the irradiated mice. Both in vitro and in vivo treatment with AM218 before irradiation improved the survival rate of CFU-GM progenitors, while no effects were observed on the CFU-S pool. This led us to postulate that the improved survival rate of the committed progenitors, at least the granulocyte-macrophage progenitors, accounts for the radioprotective capacity of AM218.

AM5, a protein-associated polysaccharide, stimulates hematopoiesis and modulates the expression of endogenous hematopoietic growth factors in murine long-term bone marrow cultures.

We have investigated the mechanism behind the hematopoietic stimulation mediated by AM5, a protein-associated polysaccharide that stimulates in vivo the murine hematopoietic system. A dose-dependent increase in hematopoietic progenitors was observed in long-term bone marrow cultures (LTBMCs) treated in vitro with AM5. The stimulatory effect was more marked in colony-forming units-granulocyte-macrophage (CFU-GM) than in CFU-spleen (CFU-S) progenitors and also more significant in the supernatant than in the adherent layer. This stimulatory effect was reversible, and continuous stimulation with high doses of AM5 was conductive to a progressive exhaustion of the culture. The analysis of the CFU-GM stimulating activity present in the supernatant of AM5-treated cultures revealed a dose-dependent induction of granulocyte-macrophage colony-stimulating activity (GM-CSA), in contrast with control cultures in which no CSA was detected. Northern blots of LTBMC-adherent layers obtained after in vitro treatment with AM5 revealed a significant mRNA expression for interleukin 1 alpha (IL-1 alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage CSF (M-CSF) and granulocyte CSF (G-CSF), in contrast with adherent layers from untreated cultures which only expressed, in detectable levels, M-CSF and stem cell factor (SCF). The SCF expression was down-modulated in AM5-treated cultures. Our results strongly suggest that the hematopoietic stimulation induced by AM5 is mediated by the modulated expression of endogenous hematopoietic growth factors.

Decrease of the plasma membrane H+-ATPase activity during late exponential growth of Saccharomyces cerevisiae.

During the last cell division of exponential growth, the H+-ATPase activity from the yeast plasma membrane decreases by a factor of two to three. This "arrest growth control" of ATPase activity is not accompanied by modification of the sensitivity to vanadate.