Differential Sensitivity of Mouse Mononuclear Phagocytes to CSF-1 and LPS: The Potentialin VivoRelevance of Enhanced IL-6 Gene Expression

Abstract

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 (PMφ) responded directly to CSF-1 compared with resident PMφ that were induced to express high levels ofIl6mRNA and release IL-6 protein. Resident PMφ released basal (constitutive) amounts of IL-6, while constitutive release by monocytes and elicited PMφ was barely detectable. Monocytes and elicited PMφ expressed similar levels of sensitivity to LPS, as measured by IL-6 release, and were less reactive than resident PMφ. When CSF-1 and LPS were added simultaneously to resident PMφ, a dose-dependent synergistic release of IL-6 was seen. Elicited PMφ 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 seenin vivowhen mice were injected with CSF-1 and LPS. Under these conditions, only resident peritoneal cells were shown to release IL-6ex vivowhile 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 responsesin vivo.