Differential expression of tumor target binding and cytolytic activities in bone marrow culture-derived macrophages

The binding and killing of a number of murine (DBA/2J) leukemia cell lines by murine bone marrow-derived macrophages (M phi s) were studied under various conditions to provide clues to the nature and specificity of tumor recognition by M phi s. Under test was the hypothesis that tumor target binding by activated M phi s is effected by saturable, high-affinity, trypsin and low temperature-sensitive receptors, whereas target binding by normal M phi s is of low affinity, nonsaturable, insensitive to low temperature and trypsin, and is believed not to be mediated by conventional receptors. The results obtained showed that this scenario was realized only rarely and that each target cell line had its own distinctive binding characteristics. Thus target binding by both unactivated and activated M phi s can be sensitive or insensitive to trypsin and low temperature depending on the target in question. This finding suggests that the binding of different targets is mediated by distinct receptors or different combinations of receptors. Contrary to previous reports, the binding of all targets tested was found to decrease with M phi activation and induction of cytotoxicity, but whatever binding strength that remained was obviously adequate for the manifestation of cytotoxicity. Fractionation of M phi s according to size (and hence maturity) revealed that tumor binding capacity (per unit surface area) increased with M phi size. Although target binding decreased in all M phi fractions after activation, it still correlated with cytotoxic activity and cell size for a given activated M phi population. Thus target binding correlates well with antitumor potential in unactivated Møs and with cytotoxic activity in activated M phi s.