Abstract: |
Modulation of granulocyte CSF (G-CSF) receptors on murine peritoneal exudate macrophages (PEM) by various cytokines was investigated. At 4°C, 125I-G-CSF receptor binding on PEM reached a plateau after 6 h and was specifically competed by unlabeled human rG-CSF but not by other cytokines, including human rCSF-1, murine recombinant granulocyte-macrophage CSF, murine rIFN-γ, human rIL-1β, and murine rTNF-α. 125I-G-CSF bound to PEM has a half-life of 30 min at 37°C. Preincubation of PEM with murine rTNF, murine recombinant granulocyte-macrophage CSF, CSF-1, or G-CSF for 30 min at 37°C resulted in partial reduction of 125I-G-CSF binding capacity, whereas IL-1 or IFN-γ did not inhibit G-CSF binding. Further studies indicated that reduction of G-CSF binding caused by TNF was a dose- and time-dependent process and did not require FCS. The reduction was transient, and receptor binding was recovered by incubation at 37°C for 8 h. The recovery of G-CSF binding was inhibited in the presence of cycloheximide. In addition, G-CSF binding studies suggested that the TNF-induced decrease in G-CSF binding to PEM was probably due to a reduction in receptor number rather than receptor affinity. Modulation of G-CSFR by TNF was also observed on nonelicited macrophages from various strains of mice. Our results demonstrate a physiologic response of G-CSFR on macrophages that is modulated by TNF. This phenomenon may play an important, as yet unknown, role in the macrophage inflammatory response. |
Keywords: |
nonhuman; animal cell; mouse; animal; mice; cells, cultured; granulocyte macrophage colony stimulating factor; mice, inbred balb c; tumor necrosis factor alpha; gamma interferon; recombinant proteins; macrophage; macrophages; interleukin 1alpha; granulocyte colony stimulating factor; ascitic fluid; colony stimulating factor 1; in vitro; tumor necrosis factor; cell surface receptor; interleukin-1; mice, inbred c3h; granulocyte-macrophage colony-stimulating factor; cycloheximide; interferon type ii; receptors, granulocyte colony-stimulating factor; priority journal; article; peritoneum exudate; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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