TY - JOUR
T1 - Analysis of the effects of tumor necrosis factor inhibitors on human hematopoiesis
AU - Ferrajoli, Alessandra
AU - Talpaz, Moshe
AU - Kurzrock, Razelle
AU - Estrov, Zeev
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - Truncated soluble fragments of tumor necrosis factor (TNF) receptors have recently been isolated from human serum and urine. These shed forms of TNF receptors bind TNF‐α and lymphotoxin and inhibit various effects of TNF in culture. In this study, we evaluated the role of these molecules in the hematopoietic system. TNF‐α and lymphotoxin inhibited colony forming units granulocyte‐macro‐phage (CFU‐GM) and burst forming units‐erythroid (BFU‐E) in a dose‐dependent fashion at concentrations ranging from 1 to 5,000 U/ml and 25 to 250 U/ ml, respectively. TNF‐α exerted a similar dose‐dependent inhibitory effect on a CD34 enriched marrow cell population, suggesting that its effect is not mediated through CD34∼ accessory ceils. Its suppressive effect was partially reversed by anti‐TNF‐α neutralizing antibodies, thus proving its specificity. Two shed forms of TNF receptors, TNF binding protein (TNF‐bp) and TNF receptor fusion protein (TNFR‐fc), had no significant effect on CFU‐GM proliferation. Both molecules, however, significantly reversed the inhibitory effect of TNF‐α (p < 0.015 and p < 0.03, respectively), whereas they had no effect on the lymphotoxin‐induced CFU‐GM growth inhibition. These results indicate that TNF‐bp and TNFR‐fc may modulate the inhibitory effects of TNF‐α in the hematopoietic system.
AB - Truncated soluble fragments of tumor necrosis factor (TNF) receptors have recently been isolated from human serum and urine. These shed forms of TNF receptors bind TNF‐α and lymphotoxin and inhibit various effects of TNF in culture. In this study, we evaluated the role of these molecules in the hematopoietic system. TNF‐α and lymphotoxin inhibited colony forming units granulocyte‐macro‐phage (CFU‐GM) and burst forming units‐erythroid (BFU‐E) in a dose‐dependent fashion at concentrations ranging from 1 to 5,000 U/ml and 25 to 250 U/ ml, respectively. TNF‐α exerted a similar dose‐dependent inhibitory effect on a CD34 enriched marrow cell population, suggesting that its effect is not mediated through CD34∼ accessory ceils. Its suppressive effect was partially reversed by anti‐TNF‐α neutralizing antibodies, thus proving its specificity. Two shed forms of TNF receptors, TNF binding protein (TNF‐bp) and TNF receptor fusion protein (TNFR‐fc), had no significant effect on CFU‐GM proliferation. Both molecules, however, significantly reversed the inhibitory effect of TNF‐α (p < 0.015 and p < 0.03, respectively), whereas they had no effect on the lymphotoxin‐induced CFU‐GM growth inhibition. These results indicate that TNF‐bp and TNFR‐fc may modulate the inhibitory effects of TNF‐α in the hematopoietic system.
KW - Hematopoiesis
KW - Lymphotoxin
KW - Tumor necrosis factor
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U2 - 10.1002/stem.5530110206
DO - 10.1002/stem.5530110206
M3 - Article
C2 - 8384506
AN - SCOPUS:0027513476
SN - 1066-5099
VL - 11
SP - 112
EP - 119
JO - STEM CELLS
JF - STEM CELLS
IS - 2
ER -