PMID- 2383651
OWN - NLM
STAT- MEDLINE
DCOM- 19900918
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 76
IP  - 4
DP  - 1990 Aug 15
TI  - The effects of tumor necrosis factor-alpha on early human hematopoietic 
      progenitor cells treated with 4-hydroperoxycyclophosphamide.
PG  - 681-9
AB  - We have previously reported that 20 hours' preincubation of human bone marrow 
      cells with interleukin-1 beta (IL-1) can protect early progenitor cells from 
      4-hydroperoxycyclophosphamide (4-HC) cytotoxicity. Since tumor necrosis 
      factor-alpha (TNF alpha) shares many of the biologic properties of IL-1, we have 
      compared the protective effects of TNF alpha with IL-1 against 4-HC. Incubation 
      of human bone marrow mononuclear cells or an enriched progenitor population for 
      20 hours with either TNF alpha or IL-1 resulted in the survival of an increased 
      number of single- and mixed-lineage colonies, including replatable blast cell 
      colonies, while only rare colonies were seen in the control group. Antibodies to 
      TNF alpha completely abolished the protection observed with IL-1, while 
      antibodies to IL-1 alpha and IL-1 beta decreased but did not abolish the 
      protection seen with TNF alpha. Combinations of low doses of TNF alpha and IL-1 
      showed synergy in their protective effects. Furthermore, no protection was 
      observed by IL-1, IL-1 bone-marrow-conditioned medium (IL-1-BMCM), or TNF alpha 
      for HL-60, K562, KG1, KG1a, and DU.528 leukemic-cell lines or primary acute 
      myelogenous leukemic (AML) blast cells from the lethal effects of 4-HC. In the 
      case of HL-60 and KG1a cell lines, TNF alpha preincubation resulted in increased 
      cytotoxicity. Furthermore, preincubation of a mixture of AML cells and normal 
      bone-marrow cells with IL-1 + TNF alpha before 4-HC resulted in the protection of 
      normal but not leukemic progenitors. These results suggest that TNF alpha is 
      necessary for the protection of normal, early, human hematopoietic progenitors 
      from 4-HC, while IL-1 is not mandatory but will synergize with TNF alpha to offer 
      increased protection. In addition, no protection from 4-HC is observed by TNF 
      alpha, IL-1, or IL-1-BMCM for primary leukemic blast cells or leukemic cell 
      lines.
FAU - Moreb, J
AU  - Moreb J
AD  - Department of Medicine, University of Florida, Gainesville.
FAU - Zucali, J R
AU  - Zucali JR
FAU - Rueth, S
AU  - Rueth S
LA  - eng
GR  - AI 24709/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Interleukin-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - U880A4FUDA (perfosfamide)
SB  - IM
MH  - Cell Line
MH  - Cyclophosphamide/*analogs & derivatives/pharmacology
MH  - Hematopoietic Stem Cells/*drug effects
MH  - Humans
MH  - Interleukin-1/pharmacology/physiology
MH  - Leukemia/blood
MH  - Tumor Necrosis Factor-alpha/*pharmacology/physiology
EDAT- 1990/08/15 00:00
MHDA- 1990/08/15 00:01
CRDT- 1990/08/15 00:00
PHST- 1990/08/15 00:00 [pubmed]
PHST- 1990/08/15 00:01 [medline]
PHST- 1990/08/15 00:00 [entrez]
AID - S0006-4971(20)82442-2 [pii]
PST - ppublish
SO  - Blood. 1990 Aug 15;76(4):681-9.