Growth factor-dependent regulation of transferrin receptor in proliferating and quiescent macrophages.
Transferrin receptor (TfR) expression in a population of murine macrophages was investigated during the colony-stimulating factor-1 (CSF-1)-induced proliferation and quiescence. Depletion of CSF-1 from the culture medium of bone marrow cell-derived macrophages (BMM) resulted in a simultaneous decrease in the total (cell surface + intracellular) amount of TfR and complete cessation of proliferating activity [( 3H]thymidine incorporation). The addition of CSF-1 to quiescent BMM resulted in a bimodal increase in surface TfR activity. A rapid but transient twofold increase only on the cell surface due to changes in the cycling of TfR was followed by a steady increase of total cellular TfR due to de novo synthesis. A similar transient increase in surface TfR was also induced by another hemopoietic colony-stimulating factor, GM-CSF, which is mitogenic for BMM. IL-3, which did not stimulate the clonal growth of these cells, failed to modulate surface TfR. In contrast to its effect on the cycling rate of TfR in quiescent cells, CSF-1 had little effect on the TfR distribution on proliferating BMM as well as on the J774 cells (a macrophage-like tumor cell line) despite the latter expressing high levels of CSF-1 receptor. This study showed that (i) cell surface modulation by growth factor is a function of state of cellular proliferation, and (ii) rapid changes in the cell surface distribution of TfR result from changes in its cycling rates.
Lokeshwar
B L
BL
Division of Radiation Oncology, Mallinckrodt Institute of Radiology, St. Louis, Missouri.
Lin
H S
HS
D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000502:physiology; D011990:Receptors, Transferrin / Q000378:metabolism*
D011990:Receptors, Transferrin; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor