Differential sensitivity of mouse mononuclear phagocytes to CSF-1 and LPS: the potential in vivo relevance of enhanced IL-6 gene expression.
In this report, we compared the responsiveness of subpopulations of mononuclear phagocytes (MNP) to the actions of the monocyte-macrophage colony-stimulating factor (CSF-1) and lipopolysaccharide (LPS), as measured by the expression of the IL-6 (Il6) gene. It was seen that neither monocytes nor elicited peritoneal macrophages (PMphi) responded directly to CSF-1 compared with resident PMphi that were induced to express high levels of Il6 mRNA and release IL-6 protein. Resident PMphi released basal (constitutive) amounts of IL-6, while constitutive release by monocytes and elicited PMphi was barely detectable. Monocytes and elicited PMphi expressed similar levels of sensitivity to LPS, as measured by IL-6 release, and were less reactive than resident PMphi. When CSF-1 and LPS were added simultaneously to resident PMphi, a dose-dependent synergistic release of IL-6 was seen. Elicited PMphi also responded synergistically but required higher levels of CSF-1 and LPS, while monocytes failed to respond synergistically under any conditions. A similar synergistic effect was also seen in vivo when mice were injected with CSF-1 and LPS. Under these conditions, only resident peritoneal cells were shown to release IL-6 ex vivo while blood leukocytes and spleen cells released minimal amounts. These findings indicate that the stage of differentiation/maturation of MNP may be important for the ability of CSF-1 to render the cells sensitive to secondary stimulation, such as by LPS, and determines to what extent MNP subpopulations contribute to inflammatory responses in vivo.
Kamdar
S J
SJ
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Chapoval
A I
AI
Phelps
J
J
Fuller
J A
JA
Evans
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D015870:Gene Expression; D018836:Inflammation Mediators / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor