Granulocyte colony-stimulating factor modulation of cytokine receptors on murine bone marrow cells. In vivo and in vitro studies.
Human recombinant granulocyte CSF (G-CSF) modulation of cytokine receptors on murine bone marrow cells (BMC) in vivo and in vitro was investigated. In vivo, G-CSF reduced 125I-G-CSF binding to BMC by greater than 95% within 30 min, with return to base line after 48 h. Human rCSF-1 binding was reduced greater than 85% after 30 min and failed to recover even after 48 h. Murine rTNF-alpha or recombinant granulocyte/macrophage CSF binding was not significantly altered. However, human rIL-1 alpha binding increased greater than 1.5-fold after 3 h, was elevated greater than 5-fold between 6 and 12 h, and declined to base line after 48 h. In vitro, G-CSF induced a greater than 1.5-fold increase in IL-1 binding to BMC after 8 h, suggesting that up-modulation of IL-1 binding in vivo required G-CSF and other influences. Further studies indicated that BMC responded to glucocorticoids and G-CSF with a synergistic increase of IL-1 binding. This synergistic IL-1R modulation was a time- and dose-dependent process and was inhibited by cycloheximide or actinomycin D in a dose-dependent manner. Binding studies further revealed that the synergistic stimulation of IL-1R expression on BMC was probably due to increased receptor number, rather than increased receptor affinity. In addition, this phenomenon was also observed in other hematopoietic cells. Our results demonstrated that G-CSF was capable of stimulating IL-1R expression on BMC both in vivo and in vitro and G-CSF in combination with glucocorticoids synergistically up-modulated IL-1 binding to BMC in vitro. Inasmuch as IL-1 induces the secretion of G-CSF and glucocorticoids in vivo, this synergistic induction may play an important, as yet unknown, role in the inflammatory cascade.
Shieh
J H
JH
James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Peterson
R H
RH
Moore
M A
MA
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D013256:Steroids / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D007375:Interleukin-1; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D013256:Steroids; D016179:Granulocyte Colony-Stimulating Factor; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide