Lithium stimulation of murine hematopoiesis in liquid culture: an effect mediated by marrow stromal cells

Quesenberry, Peter J.; Coppola, Michael A.; Gualtieri, Richard J.; Wade, Philip M.; Zhang, Song; Doukas, Michael; Shideler, Charlotte E.; Baker, Donald G.; McGrath, E

doi:10.1182/blood.v63.1.121.121

Cited by 29 publications

(8 citation statements)

References 23 publications

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“…Lithium stimulates increases in murine Dexter culture granulocytes, macrophages and megakaryocytes (Levitt and Quesenberry, 1979;Quesenberry et al, 1984;Doukas et al, 1986;McGrath et al, 1989). This is consistent with the observed increases in neutrophils and, variably, platelets seen in vivo after administration of lithium to mice or humans.…”

Section: Discussionmentioning

confidence: 56%

“…Previous studies indicate that lithium may affect in vitro Dexter hematopoiesis by inducing cytokines from adherent stromal cells (Quesenberry et al, 1984;Mc-Grath et al, 1989). Experiments employing factor dependent cell lines and antibody blocking identified GM-CSF as a stromal cytokine induced by lithium.…”

Section: Discussionmentioning

confidence: 99%

“…Lithium salts have been shown to stimulate in vivo granulocyte and probably platelet production in mice and humans (Mayfield and Brown, 1966;Bille et al, 1975;Stein et al, 1977;Rothstein et al, 1978;Lyman et al, 1980;Joyce and Chervenick, 1981;Ricci et al, 1981). We have previously shown that LiCl stimulates granulocyte, macrophage, and megakaryocyte production in long-term murine Dexter marrow culture and that pluripotent (CFU-S), granulocyte-macrophage (CFU-C), megakaryocyte (CFU-meg), and colony-forming units in diffusion chamber (CFU-D) progenitor cells are also stimulated in this setting (Levitt and Quesenberry, 1979;Quesenberry et al, 1984;Doukas et al, 1986;McGrath et al, 1989). This stimulation appeared to be a humoral, indirect one (Doukas et al, 1985) mediated via a radioresistant adherent stromal cell (Quesenberry et al, 1984).…”

mentioning

confidence: 99%

“…We have previously shown that LiCl stimulates granulocyte, macrophage, and megakaryocyte production in long-term murine Dexter marrow culture and that pluripotent (CFU-S), granulocyte-macrophage (CFU-C), megakaryocyte (CFU-meg), and colony-forming units in diffusion chamber (CFU-D) progenitor cells are also stimulated in this setting (Levitt and Quesenberry, 1979;Quesenberry et al, 1984;Doukas et al, 1986;McGrath et al, 1989). This stimulation appeared to be a humoral, indirect one (Doukas et al, 1985) mediated via a radioresistant adherent stromal cell (Quesenberry et al, 1984). Bradley and Hodgson (1979) have described a highly proliferative progenitor cell called HPP-CFC, which forms large compact colonies of over 50,000 mature macrophages in agar.…”

mentioning

confidence: 99%

“…Stromal cells from Dexter culture are known t o produce multiple stimulatory activities (Gualtieri et al, 1984). We have previously shown, using selective cell line stimulation and antibody blocking, that LiCl increases levels of GM-CSF in Dexter stromal cell cm (McGrath et al, 1989).…”

mentioning

confidence: 99%

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Lithium stimulation of HPP‐CFC and stromal growth factor production in murine dexter culture

McGrath

Wade

Kister

et al. 1992

Journal Cellular Physiology

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We have previously reported that the addition of lithium chloride (LiCl) to murine Dexter cultures results in increased numbers of progenitor and mature hematopoietic cells of the granulocyte, macrophage, and megakaryocyte lineages. We now report the effect of various levels of LiCl on the high proliferative potential colony-forming cell (HPP-CFC) in Dexter culture and on the induction of growth factors from Dexter stromal cells. LiCl (4 mEq/L) stimulated supernatant HPP-CFC for the first 4 weeks of culture (150-275%), and stimulated stromal HPP-CFC at week 3 (170-222%). Higher levels of lithium (8 and 12 mEq/L) selectively stimulated supernatant HPP-CFC, macrophage, and eosinophil production, whereas granulocytes and granulocyte-macrophage colony-forming cells (CFU-C) were inhibited. mRNA expression was evaluated from week 4 Dexter cultures that received a pulse or continuous exposure to lithium and had received either 0 or 1,100 cGy irradiation. Four mEq/L LiCl stimulated increased expression of G-CSF, GM-CSF, IL-6, and, in the nonirradiated stroma continuously exposed to lithium, CSF-1 mRNA. In general, the higher levels of lithium stimulated increased mRNA expression for these same growth factors. mRNA for the recently described Steel factor was decreased with increasing levels of lithium added to either normal or irradiated stroma. Bioassays of conditioned medium (cm) from irradiated cultures against the FDC-P1 and T1165 cell lines indicated cytokine activity, which was blocked by antibodies to GM-CSF and IL-6, respectively. Altogether these data show that lithium stimulates Dexter HPP-CFC, and this stimulation appears to be mediated by multiple growth factors that are induced from stromal cells.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lithium stimulation of HPP‐CFC and stromal growth factor production in murine dexter culture

McGrath

Wade

Kister

et al. 1992

Journal Cellular Physiology

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Collagen synthesis by murine bone marrow cell culture

Waterhouse

Quesenberry

Balian

1986

Journal Cellular Physiology

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Collagen types synthesized by murine bone marrow cells were studied and the effect of lithium chloride on collagen biosynthesis in vitro was investigated. In the liquid culture system used, an adherent, mixed cell population supports hemopoiesis. Radioactive labeling of cell cultures and subsequent fractionation with ammonium sulfate, enzyme digestion, immune precipitation, and gel electrophoresis indicated that the bone marrow cells synthesized precursors to collagen types I, III, and IV, and fibronectin. A previously undescribed molecule or fragment with an apparent molecular weight of 17,000 daltons that was susceptible to bacterial collagenase and containing no interchain disulfide bonds was also identified in the culture media of both control and lithium-treated cells. Lithium treatment did not affect the types of collagen synthesized, although the relative proportions of collagen types may differ from controls. However, lithium does have an effect on the appearance of some, as yet unidentified, non-collagenous components in the cell culture media.

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Lithium stimulation of diffusion chamber colony growth is mediated by factors other than colony‐stimulating factor

Doukas

Shadduck

Waheed

et al. 1989

The International Journal of Cell Cloning

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Lithium is a recognized, potent stimulator of granulopoiesis. The present study used the model of clonal growth of granulopoietic precursors in diffusion chambers to investigate the relevance of certain colony-stimulating factors to lithium stimulation in vivo. In this system, lithium stimulation of granulopoiesis could not be attributed to changes in serum or chamber fluid colony-stimulating factor levels. Antibody to colony-stimulating factor-1 administered during culture markedly reduced morphologic expression of colonies in control and lithium-pretreated host mice, yet subculture of chamber contents revealed that lithium stimulation of a granulopoietic progenitor, perhaps of primitive potentiality, had nevertheless occurred. Therefore, we hypothesize that lithium acts in an indirect, hormonal fashion and that these colony-stimulating factors, while necessary for morphologic expression, play no role in the stimulatory effect. This hypothesis raises the possibility that lithium in combination with recombinant colony-stimulating factors may result in clinically effective synergistic stimulation of granulopoiesis.

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Lithium stimulation of murine hematopoiesis in liquid culture: an effect mediated by marrow stromal cells

Cited by 29 publications

References 23 publications

Lithium stimulation of HPP‐CFC and stromal growth factor production in murine dexter culture

Lithium stimulation of HPP‐CFC and stromal growth factor production in murine dexter culture

Collagen synthesis by murine bone marrow cell culture

Lithium stimulation of diffusion chamber colony growth is mediated by factors other than colony‐stimulating factor

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