The activation state of macrophage subpopulations from a murine fibrosarcoma

Abstract

We have separated subpopulations of macrophages from an immunogenic fibrosarcoma by the technique of unit gravity velocity sedimentation. The activation state of these subpopulations was determined by measurement of the Fc receptor avidity of adherent cells, and by their 5′ nucleotidase and acid phosphatase activity. The subpopulations were compared to resident peritoneal macrophages and the peritoneal macrophage subpopulations elicited by injection of proteose peptone or C. parvum. The results show that two macrophage subpopulations exist within the tumour. The smaller, peroxidase-positive population, with a sedimentation velocity of 1-5 mm/h, is similar to proteose peptonestimulated macrophages with respect to Fc receptor expression, while the other, rapidly sedimenting population (5-9 mm/h) is partially activated. However, neither population achieved the level of activation demonstrated by rapidly sedimenting, C. parvum-activated macrophages. Analysis of the enzyme activity of rapidly adherent macrophages indicated that tumour, proteose peptone or C. parvum macrophages were all activated when compared to resident peritoneal macrophages. No significant differences were found with respect to the elevated levels of acid phosphatase in the three activated macrophage populations, but the 5′ nucleotidase activity of C. parvum-elicited macrophages was significantly lower than either the proteose peptone or tumour macrophages. This again demonstrated that the tumour macrophages were less activated than C. parvum macrophages. These data show that tumour-infiltrating macrophages are a heterogeneous population composed of at least two subpopulations existing in different activation states and that within the tumour microenvironment they are not capable of differentiating to the higher activation state, demonstrated by C. parvum macrophages.