Expression of gamma-interferon receptor in murine bone marrow-derived macrophages associated with macrophage differentiation: Evidence of gamma-interferon receptors in the regulation of macrophage proliferation
✍ Scribed by Ben D.-M. Chen; Ta-Hsu Chou; Voravit Ratanatharathorn
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 887 KB
- Volume
- 133
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
The effect of purified, recombinant murine gamma interferon (IFN-7) on the regulation of macrophage proliferation induced by colony-stimulating factor 1 (CSF-1) was investigated. Although both hemopoietic stem cells (GM-CFC) and tissue-derived peritoneal exudate macrophages (PEM) proliferated in response to CSF-1, the more mature PEM were much more sensitive to an antiproliferative effect of IFN-7. The role of IFN-7 receptor expression and its relationship to growth inhibition was examined. Bone marrow cells as a whole did not exhibit an appreciable amount of IFN-7 receptor binding activity. Likewise, nonadherent (NA) cells derived from CSF-I-stimulated bone marrow cultures displayed low levels of IFN-7 receptor binding activity. On the contrary, more mature adherent (AD) cells (monocytes/macrophages) from t h e same culture exhibited high levels of IFN-7 receptor binding activity, which continued to increase with culture time. The elevated IFN-7 binding activity is due to an increase in total receptor number rather than the binding affinity as judged by Scatchard analysis. Similar to the relationship between PEM and GM-CFC, more mature AD cells were also more susceptible to the inhibitory effect of IFN-y on CSF-I-induced proliferation than their less mature NA counterparts. The fact that the sensitivity to IFN-7 correlated well with the expression of existing IFN-y receptors strongly suggests that the inhibitory effect is mediated through 1FN-y receptors. This study shows that the expression of IFN-7 receptors in mononuclear phagocytes may not only represent one of the phenotypic parameters acquired by the growing macrophages during the process of differentiation, but may play some role in controlling proliferation.
Mature macrophages are derived from bone marrow myeloid stem cells via blood monocytes by a very complicated process involving both cell replication and differentiation. A group of specific hematopoietic growth factors, known as colony-stimulating factors (CSFs), are required for the growth and production of mature end cells from primary cultures of bone marrow stem cells. Among this group of growth factors, CSF-1 (or M-CSF) derived from L-cell conditioned medium (LCM) stimulates predominantly macrophage production by bone marrow granulocyte-macrophage progenitor cells (GM-CFC) (Stanley and Guilbert, 1981;Metcalf, 1986) and by a subpopulation of relatively mature, unipotential, macrophage colony-forming cells (M-CFC) present in various tissue sources, including inflammatory exudate, lung, liver, spleen, thymus, and circulating blood (monocytes) (Stewart, 1980;Stanley et al., 1978). CSF-1 may also be responsible for the induction of macrophage differentiation as evidenced by the observation that nonadherent 0 1987 ALAN R. LISS, INC.
mononuclear phagocyte precursor cells were rapidly transformed into the adherent, proliferating macrophages in vitro in response to' purified CSF-1 (Tushinski et al.