DIFFERENTIAL SENSITIVITY OF MOUSE MONONUCLEAR PHAGOCYTES TO CSF-1 ANDLPS - THE POTENTIAL IN-VIVO RELEVANCE OF ENHANCED IL-6 GENE-EXPRESSION

In this report, we compared the responsiveness of subpopulations of mo nonuclear phagocytes (MNP) to the actions of the monocyte-macrophage c olony-stimulating factor (CSF-1) and lipopolysaccharide (LPS), as meas ured by the expression of the IL-6 (Il6) gene. It was seen that neithe r monocytes nor elicited peritoneal macrophages (PM phi) responded dir ectly to CSF-1 compared with resident PM phi that were induced to expr ess high levels of Il6 mRNA and release IL-6 protein. Resident PM phi released basal (constitutive) amounts of IL-6, while constitutive rele ase by monocytes and elicited PM phi was barely detectable. Monocytes and elicited PM phi expressed similar levels of sensitivity to LPS, as measured by IL-6 release, and were less reactive than resident PM phi . When CSF-1 and LPS were added simultaneously to resident PM phi, a d ose-dependent synergistic release of IL-6 was seen. Elicited PM phi al so responded synergistically but required higher levels of CSF-1 and L PS, while monocytes failed to respond synergistically under any condit ions. A similar synergistic effect was also seen in vivo when mice wer e injected with CSF-1 and LPS. Under these conditions, only resident p eritoneal cells were shown to release IL-6 er vivo while blood leukocy tes 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 st imulation, such as by LPS, and determines to what extent MNP subpopula tions contribute to inflammatory responses in vivo. (C) 1996 Academic Press, Inc.