TY - JOUR
T1 - Differential sensitivity of mouse mononuclear phagocytes to CSF-1 and LPS
T2 - The potential in vivo relevance of enhanced IL-6 gene expression
AU - Kamdar, Sonya J.
AU - Chapoval, Andrei I.
AU - Phelps, Jessica
AU - Fuller, Jane A.
AU - Evans, Robert
N1 - Funding Information:
This publication was supported by U.S. Public Health Service Grant CA27523 and The Jackson Laboratory Cancer Center Grant CA34196 awarded by the National Cancer Institute. The Jackson Laboratory is fully accredited by the American Association for the Accreditation for Laboratory Animal Care. The authors express their appreciation to Drs.Ed Leiter, Sung-don Yang, and David Serreze for their insightful comments.
PY - 1996/12/15
Y1 - 1996/12/15
N2 - 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 of Il6 mRNA 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 PM∅. 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 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.
AB - 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 of Il6 mRNA 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 PM∅. 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 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.
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U2 - 10.1006/cimm.1996.0306
DO - 10.1006/cimm.1996.0306
M3 - Article
C2 - 8954616
AN - SCOPUS:0030589675
SN - 0008-8749
VL - 174
SP - 165
EP - 172
JO - Cellular Immunology
JF - Cellular Immunology
IS - 2
ER -