Interleukin 3 promotes the in vitro proliferation of murine pluripotent hematopoietic stem cells.

Spivak, Jerry L.; Smith, Robert R.; Ihle, JN

doi:10.1172/jci112145

Cited by 92 publications

(33 citation statements)

References 36 publications

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“…1). When either IL 3 at a concentration of 20 U/ml or the tumor promoter phorbol myristate acetate (PMA, 10-7 M) was added at the start of the incubation, the initial decline in total cell number was more marked over the first 24 h than in the control cultures (P < 0.001), but thereafter the number of cells per flask reached a plateau that remained constant for PMA for up to 144 h of culture; for IL 3, as we have previously reported (10), cell number began to increase after 96 h of culture.…”

Section: Resultssupporting

confidence: 54%

“…We have previously observed that under the culture conditions used, IL 3 promoted the in vitro proliferation of day 11 CFU-S only in the nonadherent population of the cultured marrow cells (10). When marrow cells cultured in the presence of 1-0 M PMA for 72 h were assayed separately for day 11 CFU-S as adherent and nonadherent cell populations, on average less than one colony per spleen was recovered from the adherent cell population, a frequency not different from that obtained for endogenous spleen colony formation.…”

Section: Resultsmentioning

confidence: 96%

“…The mechanisms governing the proliferation of CFU-S are not well understood, but recently it was demonstrated that IL 3 supports the proliferation of these cells in vitro (10). In this study, we examined interaction of tumor-promoting phorbol esters on the in vitro survival of CFU-S and the effect of these agents on the interaction between IL 3 and CFU-S in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…CFU-S were assayed by the method ofTill and McCulloch (13) as previously described (10). Briefly, syngeneic recipient mice were exposed to a lethal (1,050 rad) dose of whole body irradiation from a '37Cesium source (dose rate 126 rad/min, gamma cell 40, Atomic Energy of Canada, Ottawa, Canada).…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, the range of known target cell interactions for the phorbol esters amongst hematopoietic progenitor cells is similar to that of IL 3, suggesting that both of these agents may interact with such cells through similar mechanisms. We and others have recently demonstrated that IL 3 promotes the in vitro proliferation of pluripotent hematopoietic stem cells (CFU-S) (2,(10)(11)(12). In this report, we describe the effect of tumor-promoting phorbol esters on CFU-S survival in vitro and the interaction of these agents with IL 3.…”

Section: Introductionmentioning

confidence: 99%

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Tumor-promoting phorbol esters support the in vitro proliferation of murine pluripotent hematopoietic stem cells.

Spivak¹,

Hogans²,

Stuart³

1989

J. Clin. Invest.

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The effect of tumor-promoting phorbol esters on the in vitro proliferation of mouse pluripotent hematopoietic stem cells (CFU-S) was examined using a short-term in vitro culture system and an 11-d spleen colony assay. Phorbol myristate acetate (PMA, 10-7 M), but not the inert compound phorbol, supported the in vitro survival of day 11 CFU-S for 72 h in a manner similar to IL 3. PMA also enhanced the effect of IL 3 on the in vitro survival of day 11 CFU-S and as little as 1 h of exposure to PMA was sufficient for this purpose. The effect of PMA on CFU-S survival in vitro was not mediated by prostaglandins, did not require an established adherent cell population, and was observed at a concentration of 10-M. PMA alone did not enhance the in vitro survival of day 11 CFU-S at very low concentrations of FCS but was still able to potentiate the effect of IL 3 on these cells. PMA also enhanced the in vitro survival of day 11 CFU-S from mice treated with 5-fluorouracil or from marrow cells exposed to merocyanine 540 and light. The interaction of PMA with day 11 CFU-S was not inhibited by a neutralizing antiserum to IL 3 but was inhibited by the protein kinase inhibitor H-7. Together, the data indicate that tumor-promoting phorbol esters interact with pluripotent hematopoietic stem cells. Like IL 3, their effect appears to be permissive and involves stem cells with marrow repopulating ability.

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Section: Resultssupporting

confidence: 54%

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tumor-promoting phorbol esters support the in vitro proliferation of murine pluripotent hematopoietic stem cells.

Spivak¹,

Hogans²,

Stuart³

1989

J. Clin. Invest.

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In vivo effect of murine recombinant interleukin 3 on early hemopoietic progenitors

1987

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Normal and irradiated mice were perfused with recombinant interleukin 3 (rIL3) and the number of early hemopoietic progenitors (CFU-S) was quantified in different organs. Normal mice perfused with rIL3 for 3 or 7 days showed a dramatic increase in the number of CFU-S in the spleen, liver and blood, while the bone marrow CFU-S number was slightly decreased. The total number of CFU-S per animal was only slightly increased; the major effect of rIL3 perfusion was thus on the distribution of CFU-S in the mice. Lethally irradiated mice injected with 5 X 10(4) syngeneic bone marrow cells and perfused with rIL3 were killed after 10 days. A significant increase in both the number and size of the splenic colonies was observed. The CFU-S content of these colonies, determined in a second set of irradiated mice, was increased by more than 25-fold, indicating that in conditions of hemopoietic depletion, rIL3 vastly increased the self-renewal capacity of early progenitors.

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Characterization of granulocytes and mast cells in cultures of mouse bone marrow stimulated with interleukin‐3

Bender

Epps

Stewart

1988

Journal Cellular Physiology

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Bone marrow cells in liquid culture with interleukin 3 produce a population of non-adherent granulocytes and mast cells. Flow cytometry was used to identify granulocytes and mast cells on the basis of the physical properties of perpendicular light scatter (PLS) and coulter volume (CV) as well as the expression IgE and CR3 receptors. Multicolor analysis indicated there were subpopulations of Thy1.2 positive cells which transiently appeared in these cultures and also expressed IgE receptors, CR3 receptors or neither of these receptors. The data suggested a differentiation scheme in which Thy1.2 positive precursor cells give rise to granulocytes and mast cells. Further evidence for this differentiation scheme was provided from CV vs. PLS distributions which showed increases in CV and PLS as Thy1.2 positive cells differentiated into mast cells and decreases in CV and PLS as Thy1.2 positive cells differentiated into granulocytes.

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Interleukin 3 promotes the in vitro proliferation of murine pluripotent hematopoietic stem cells.

Abstract: Medium conditioned by activated T lymphocytes stimulates the in vitro proliferation of pluripotent hematopoietic stem cells

Cited by 92 publications

References 36 publications

Tumor-promoting phorbol esters support the in vitro proliferation of murine pluripotent hematopoietic stem cells.

Tumor-promoting phorbol esters support the in vitro proliferation of murine pluripotent hematopoietic stem cells.

In vivo effect of murine recombinant interleukin 3 on early hemopoietic progenitors

Characterization of granulocytes and mast cells in cultures of mouse bone marrow stimulated with interleukin‐3

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