The binding of tumor cells by murine mononuclear phagocytes can be divided into two qualitatively distinct types.

Peritoneal macrophages from C57BL/6N mice infected with BCG have a greater capacity for tumor cell binding than do inflammatory macrophages elicited by several agents. To determine if these quantitatively distinct types of binding were qualitatively distinct as well, we compared them in several ways. Scanning electron microscopy of macrophage-tumor cell interactions reveals clustering of 2 to 5 tumor targets on the central portion of BCG-activated macrophages, in contrast to the very few tumor cells found at the periphery of inflammatory macrophages. Tumor cell binding to BCG-activated macrophages required divalent cations and trypsin-sensitive surface structures on the macrophages, but the low-level binding to inflammatory macrophages required neither. The ability of trypsinized BCG-activated macrophages to bind P815 tumor targets was recovered with time in culture. BCG-activated macrophages required intact energy metabolism, microfilaments, and microtubules to complete augmented tumor cell binding, whereas inflammatory macrophages did not. Targets bound to BCG macrophages could be competitively removed by addition of large excesses of unlabeled tumor cells, but targets bound to inflammatory macrophages could not be so removed. Tumor cells labeled with 111Indium oxine were used to estimate the specific (i.e., competitively inhibitable) and nonspecific (noncompetitively inhibitable) components of binding. Binding of P815 tumor cells to BCG-activated macrophages was predominantly specific, whereas their binding to inflammatory macrophages was predominantly nonspecific. Binding by activated or inflammatory macrophages of lymphocytes or by transformed 3T3 cells of neoplastic or non-neoplastic targets was also nonspecific. Binding by BCG-elicited macrophages from A/J mice, previously demonstrated to be quantitatively deficient in binding ability, was qualitatively similar to that to inflammatory macrophages and was not competitively inhibitable. The data suggest that tumor cell binding by activated macrophages is qualitatively as well as quantitatively distinct from binding to inflammatory macrophages.