+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Tumor necrosis factor-alpha strongly potentiates interleukin-3 and granulocyte-macrophage colony-stimulating factor-induced proliferation of human CD34+ hematopoietic progenitor cells



Tumor necrosis factor-alpha strongly potentiates interleukin-3 and granulocyte-macrophage colony-stimulating factor-induced proliferation of human CD34+ hematopoietic progenitor cells



Blood 75(12): 2292-2298



Previous studies have shown that tumor necrosis factors (TNFs) inhibit the proliferative effects of crude or purified colony-stimulating factors (CSFs) on low density human bone marrow cell fractions. In the present study we investigated the effects of TNF alpha on the growth of highly purified CD34+ human hematopoietic progenitor cells (HPC) in response to recombinant CSFs. In short-term liquid cultures (5 to 8 days), TNF alpha strongly potentiates interleukin-3 (IL-3) and granulocyte-macrophage-CSF (GM-CSF)-induced growth of CD34+ HPC, while it has no proliferative effect per se. Within 8 days, the number of viable cells obtained in TNF alpha-supplemented cultures is threefold higher than in cultures carried out with IL-3 or GM-CSF alone. Secondary liquid cultures showed that the potentiating effect of TNF alpha on IL-3-induced proliferation of CD34+ HPC does not result from an IL-3-dependent generation of TNF alpha responsive cells. Limiting dilution analysis indicates that TNF alpha increases both the frequency of IL-3 responding cells and the average size of the IL-3-dependent clones. The potentiating effect of TNF alpha on IL-3- and GM-CSF-dependent growth of CD34+ HPC is also observed in day 7 colony assays. Under these short-term culture conditions, TNF alpha does not appear to accelerate cell maturation as a precursor morphology is retained. Finally, TNF alpha inhibits the relatively weak growth-promoting effect of granulocyte-CSF (G-CSF), which acts on a more committed subpopulation of CD34+ HPC different from that recruited by IL-3 and GM-CSF. TNF beta displays the same modulatory effects as TNF alpha. Thus, TNFs appear to enhance the early stages of myelopoiesis.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 041873426

Download citation: RISBibTeXText

PMID: 1693526


Related references

Interleukin-11 stimulates the proliferation of human hematopoietic CD34+ and CD34+CD33-DR- cells and synergizes with stem cell factor, interleukin-3, and granulocyte-macrophage colony-stimulating factor. Experimental Hematology 21(13): 1668-1672, 1993

The effect of macrophage-colony stimulating factor and other humoral factors (interleukin-1, -3, -6, and -11, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor) on human osteoclast formation from circulating cells. Bone 28(3): 261-267, 2001

Interleukin-3 in cooperation with transforming growth factor beta induces granulocyte macrophage colony stimulating factor independent differentiation of human CD34+ hematopoietic progenitor cells into dendritic cells with features of Langerhans cells. Journal of Investigative Dermatology 121(6): 1397-1401, 2003

Interleukin-17 augments tumor necrosis factor-alpha-induced granulocyte and granulocyte/macrophage colony-stimulating factor release from human colonic myofibroblasts. Journal of Gastroenterology 40(8): 802-810, 2005

Interleukin 1 and/or tumor necrosis factor-alpha synergize with granulocyte-macrophage colony-stimulating factor to enhance histamine synthesis in hematopoietic cells: role of prostaglandin E2. European Journal of Immunology 19(11): 1999-2003, 1989

Macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 induces the differentiation of CD34+ hematopoietic progenitor cells into Langerhans cells under serum-free conditions without granulocyte-macrophage colony-stimulating factor. Journal of Investigative Dermatology 120(2): 256-265, 2003

Recombinant human stem cell factor enhances the formation of colonies by CD34+ and CD34+lin- cells, and the generation of colony-forming cell progeny from CD34+lin- cells cultured with interleukin-3, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Blood 77(11): 2316-2321, 1991

CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to granulocyte-macrophage colony-stimulating factor plus tumor necrosis factor alpha: II. Functional analysis. Blood 90(4): 1458-1470, 1997

Low-dose granulocyte colony-stimulating factor combined with granulocyte-macrophage colony-stimulating factor for mobilizing peripheral CD34+ hematopoietic progenitor cells. Di 1 Jun Yi Da Xue Xue Bao 24(9): 1051-1052, 2004

Production of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor by human mononuclear cells stimulated with granulocyte-macrophage colony-stimulating factor. Blood 72(4): 1368-1374, 1988

Induction of dendritic cell differentiation by granulocyte-macrophage colony-stimulating factor, stem cell factor, and tumor necrosis factor alpha in vitro from lineage phenotypes-negative c-kit+ murine hematopoietic progenitor cells. Blood 90(12): 4842-4853, 1997

Treatment of BCL-1 murine B-cell leukemia with recombinant cytokines. Comparative analysis of the anti-leukemic potential of interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and their combination. Leukemia and Lymphoma 7(1-2): 79-86, 1992

Interdependence of the radioprotective effects of human recombinant interleukin 1 alpha tumor necrosis factor alpha granulocyte colony stimulating factor and murine recombinant granulocyte macrophage colony stimulating factor. Journal of Immunology 140(1): 108-111, 1988

All-trans retinoic acid directly inhibits granulocyte colony-stimulating factor-induced proliferation of CD34+ human hematopoietic progenitor cells. Blood 84(9): 2940-2945, 1994

Additive effects of interleukin 1 and tumor necrosis factor alpha on the accumulation of the three granulocyte and macrophage colony stimulating factor messenger rna species in human endothelial cells. EMBO (European Molecular Biology Organization) Journal 6(8): 2261-2266, 1987