Interferon-γ exerts its negative regulatory effect primarily on the earliest stages of murine erythroid progenitor cell development
✍ Scribed by Chang Q. Wang; Kodetthoor B. Udupa; David A. Lipschitz
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 603 KB
- Volume
- 162
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
Interferon-y (INFy) 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 INFy 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. INFy 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 INFy addition was delayed after culture initiation. The effects of INFy on BFU-E did not require the presence of interleukin-la (IL-la), tumor necrosis factor-a (TNFa), or granulocyte macrophage colony stimulating factor (GM-CSF), as its effects were not neutralized by monoclonal antibodies against IL-I a, TNFa, or GM-CSF. This applied whether INFy was added to culture with individual antibodies or with a combination of all three antibodies. INFy was not required for I L -l a -or TNFa-induced suppression of BFU-E, as their effects were not neutralized by a monoclonal anti-INFy antibody. In contrast, GM-CSF-induced suppression of BFU-E was negated by the simultaneous addition of anti-INFy. We have previously shown that the addition of TNFa does not suppress BFU-E growth in cultures from marrow depleted of macrophages. Suppression did occur, however, if a small concentration of INFy that does not inhibit and increasing concentrations of TNFa were added to culture, suggesting a synergistic effect between INFy and TNFa. These observations suggest that INFy 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. INFy is also involved in GM-CSF-induced inhibition of BFU-E colony growth.