PMID- 14745429
OWN - NLM
STAT- MEDLINE
DCOM- 20040930
LR  - 20171116
IS  - 1466-4860 (Print)
IS  - 1466-4860 (Linking)
VI  - 5
IP  - 1
DP  - 2004
TI  - In vitro effects of interferon-gamma and tumor necrosis factor-alpha on CD34+ 
      bone marrow progenitor cells from aplastic anemia patients and normal donors.
PG  - 39-46
AB  - Acquired aplastic anemia is characterized by loss or dysfunction of hematopoietic 
      stem and progenitor cells. The proinflammatory cytokines Tumor necrosis 
      factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) may be responsible for 
      the immune-mediated pathology observed in some patients. The CD34+ population of 
      bone marrow mononuclear cells contains primitive cells responsible for 
      hemopoiesis. We investigated the response of CD34+ cells from aplastic anemia 
      patients to a combination of IFN-gamma and TNF-alpha, and compared them to cells 
      from normal volunteer donors. This was to determine whether aplastic CD34+ cells 
      are more sensitive than normal cells to IFN-gamma/TNF-alpha-mediated effects, and 
      whether cytokine-induced CD95 expression can explain the high levels of apoptosis 
      observed in CD34+ cells from aplastic patients. CD34+38- cells were most affected 
      by overnight incubation with these cytokines, their proportion and numbers being 
      reduced in both normal donors and patients. There was no evidence for increased 
      apoptosis, suggesting that this effect may be due to differentiation. 
      IFN-gamma/TNF-alpha induced upregulation of CD95 on both normal and aplastic 
      CD34+ cells, although the basal level of CD95 expression was increased in 
      aplastic cells. However, CD95 induction did not make cells from normal donors or 
      aplastic anemia patients susceptible to induction of apoptosis by agonistic 
      anti-CD95 antibodies, soluble CD95 ligand, or membrane-bound CD95L. In vivo CD95L 
      is required for CD95 induced apoptosis. No forms of this protein were detectable 
      in lymphocytes from aplastic patients. We conclude that increased apoptosis in 
      aplastic CD34+ cells is not due to increased sensitivity to IFN-gamma/TNF-alpha. 
      We further show that normal and aplastic CD34+ cells are resistant to CD95 
      apoptosis, even in the presence of mCD95L.
FAU - Welsh, Jonathan P
AU  - Welsh JP
AD  - Department of Haematology, St George's Hospital Medical School, London, UK. 
      jwelsh@sghms.ac.uk
FAU - Rutherford, Timothy R
AU  - Rutherford TR
FAU - Flynn, Julie
AU  - Flynn J
FAU - Foukaneli, Theodora
AU  - Foukaneli T
FAU - Gordon-Smith, Edward C
AU  - Gordon-Smith EC
FAU - Gibson, Frances M
AU  - Gibson FM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hematol J
JT  - The hematology journal : the official journal of the European Haematology 
      Association
JID - 100965523
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD34)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Anemia, Aplastic/*pathology
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antigens, CD34
MH  - Apoptosis
MH  - Bone Marrow Cells/pathology
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Hematopoietic Stem Cells/*drug effects/*pathology
MH  - Humans
MH  - Interferon-gamma/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Up-Regulation/drug effects
MH  - fas Receptor/biosynthesis/immunology
EDAT- 2004/01/28 05:00
MHDA- 2004/10/01 05:00
CRDT- 2004/01/28 05:00
PHST- 2004/01/28 05:00 [pubmed]
PHST- 2004/10/01 05:00 [medline]
PHST- 2004/01/28 05:00 [entrez]
AID - 6200340 [pii]
AID - 10.1038/sj.thj.6200340 [doi]
PST - ppublish
SO  - Hematol J. 2004;5(1):39-46. doi: 10.1038/sj.thj.6200340.