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Modulation of hematopoietic colony formation of stem cells in peripheral blood by anti-TGF-β in patients with severe immunosuppression

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Summary

The influence of transforming growth factor-β (TGF-β) on hematopoiesis has been evaluated by adding blocking antibodies against TGF-β to colony forming assays (CFU-c). When optimum concentrations of recombinant growth factors, granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin-3 (IL-3) were added to stem cells from the peripheral blood of healthy individuals and certain patients with tumors or HIV infection, the anti-TGF-β capable of blocking 5 ng/ml of active TGF-β had no significant influence on erythroid or myeloid colony formation. However, in certain immunosuppressed individuals, anti-TGF-β resulted in a significant decrease of erythroid colony formation and slight suppression of myeloid colony formation. The significant inhibition of hematopoiesis by plasma of HIV patients could be due to the presence of active forms of TGF-β. The results of the blocking experiments are consistent with the concept that TGF-β in low concentrations is essential for erythropoiesis and myelopoiesis but that higher levels of TGF-β primarily inhibit erythropoiesis in vitro. TGF-β serves as a coordinating factor when efficient recruitment of granulocytes and monocytes is more essential than erythropoiesis and stem cell growth.

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Abbreviations

BFU-E:

burst forming unit-erythroid

CFC:

colony forming cells

CFU-GEMM:

colony forming unit-granulocyte/erythroid/macrophage/megacaryocyte

CFU-GM:

colony forming unit-granulocyte/macrophage

EPO:

erythropoietin

GM-CSF:

granulocyte/macrophage-colony stimulating factor

HIV:

human immunodeficiency virus

IL-1:

interleukin-1

IL-3:

interleukin-3

IMDM:

Iscove's Modified Dulbecco's medium

PBS:

phosphate buffered saline

TGF-β :

transforming growth factor-β

TNF-α :

tumor necrosis factor-α

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Authors and Affiliations

  1. Institut für Blutgerinnung und Transfusionsmedizin, Immunologisches Labor, Heinrich Heine Universität, Düsseldorf

    B. Harms, G. Kögler, P. Wernet, H. T. Brüster & E. M. Schneider

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  1. B. Harms
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  2. G. Kögler
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  3. P. Wernet
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  4. H. T. Brüster
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  5. E. M. Schneider
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Harms, B., Kögler, G., Wernet, P. et al. Modulation of hematopoietic colony formation of stem cells in peripheral blood by anti-TGF-β in patients with severe immunosuppression. Klin Wochenschr 69, 1139–1145 (1991). https://doi.org/10.1007/BF01815431

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  • DOI: https://doi.org/10.1007/BF01815431

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