In vivo administration of recombinant human interleukin-1 and macrophage colony-stimulating factor (M-CSF) induce a rapid loss of M-CSF receptors in mouse bone marrow cells and peritoneal macrophages: effect of administration route.
Earlier studies suggested the existence of a blood-bone marrow barrier that significantly inhibits the transfer of plasma macrophage colony-stimulating factor (M-CSF) to responsive hematopoietic cells in vivo as indicated by its failure to induce a receptor downregulation in bone marrow cells. In this study, the effect of recombinant human interleukin-1 (rhuIL-1) was investigated. In vivo administration of rhuIL-1, either intraperitoneally (IP) or intravenously (IV), induced a rapid transient loss of M-CSF receptor binding activity in bone marrow cells, with a nadir occurring between 2 to 4 hours while loss of M-CSF receptors by cells in the peritoneal cavity occurred only in animals receiving rhuIL-1 via IP administration. The loss of M-CSF receptor activity after rhuIL-1 treatment was correlated with an elevated level of circulating M-CSF. However, the loss of M-CSF receptors in marrow cells was prevented by dexamethasone (Dex) treatment before rhuIL-1 administration. The fact that Dex treatment also reduced the level of circulating M-CSF after rhuIL-1 administration suggests that the inhibitory effects of IL-1 are mediated through locally produced M-CSF. Administration of rhuM-CSF at higher doses, either IV or IP, also induced a loss of M-CSF receptor of lesser degree in the marrow cells. However, the loss of M-CSF receptors by the peritoneal cells was induced only in mice receiving rhuM-CSF through IP administration. Taken together, these results indicate the existence of a unidirectional barrier that prevents the transfer of blood M-CSF and IL-1 to peritoneal cavity but not vice versa.
Chen
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BD
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201.
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D010529:Peritoneal Cavity / Q000166:cytology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins; D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor