PMID- 7814445
OWN - NLM
STAT- MEDLINE
DCOM- 19950203
LR  - 20081121
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 162
IP  - 1
DP  - 1995 Jan
TI  - Interferon-gamma exerts its negative regulatory effect primarily on the earliest 
      stages of murine erythroid progenitor cell development.
PG  - 134-8
AB  - Interferon-gamma (INF-gamma) has been shown to suppress erythropoiesis and 
      perhaps to contribute to the anemia of chronic disease. In this study we 
      demonstrated that the concentration of INF gamma required to suppress murine 
      burst forming unit-erythroid (BFU-E) growth was significantly less than that 
      required to suppress colony forming unit-erythroid (CFU-E) growth. INF gamma 
      acted at the most primitive step in erythroid progenitor cell differentiation and 
      proliferation, as inhibition was maximal when added at the time of BFU-E culture 
      initiation. Inhibition was progressively less if INF gamma addition was delayed 
      after culture initiation. The effects of INF gamma on BFU-E did not require the 
      presence of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF 
      alpha), or granulocyte macrophage colony stimulating factor (GM-CSF), as its 
      effects were not neutralized by monoclonal antibodies against IL-1 alpha, TNF 
      alpha, or GM-CSF. This applied whether INF gamma was added to culture with 
      individual antibodies or with a combination of all three antibodies. INF gamma 
      was not required for IL-1 alpha- or TNF alpha-induced suppression of BFU-E, as 
      their effects were not neutralized by a monoclonal anti-INF gamma antibody. In 
      contrast, GM-CSF-induced suppression of BFU-E was negated by the simultaneous 
      addition of anti-INF gamma. We have previously shown that the addition of TNF 
      alpha does not suppress BFU-E growth in cultures from marrow depleted of 
      macrophages. Suppression did occur, however, if a small concentration of INF 
      gamma that does not inhibit and increasing concentration of TNF alpha were added 
      to culture, suggesting a synergistic effect between INF-gamma and TNF alpha. 
      These observations suggest that INF gamma is a potent direct inhibitor of 
      erythroid colony growth in vitro. It exerts its negative regulatory effect 
      primarily on the earliest stages of erythroid progenitor cell differentiation and 
      proliferation, as much higher doses are required to suppress late erythroid cell 
      development. INF gamma is also involved in GM-CSF-induced inhibition of BFU-E 
      colony growth.
FAU - Wang, C Q
AU  - Wang CQ
AD  - Geriatric Research Education and Clinical Center (GRECC), John L. McClellan 
      Memorial Veterans Hospital, Little Rock, Arkansas 72205.
FAU - Udupa, K B
AU  - Udupa KB
FAU - Lipschitz, D A
AU  - Lipschitz DA
LA  - eng
GR  - R01-AG 09458/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Antibodies)
RN  - 0 (Interleukin-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Antibodies/analysis/immunology/pharmacology
MH  - Cell Differentiation/drug effects/physiology
MH  - Cell Division/drug effects/physiology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Erythroid Precursor Cells/*cytology/drug effects/physiology
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating 
      Factor/immunology/pharmacology/physiology
MH  - Interferon-gamma/*pharmacology
MH  - Interleukin-1/immunology/pharmacology/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Tumor Necrosis Factor-alpha/immunology/pharmacology/physiology
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 10.1002/jcp.1041620116 [doi]
PST - ppublish
SO  - J Cell Physiol. 1995 Jan;162(1):134-8. doi: 10.1002/jcp.1041620116.