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Morphological Evidence for the Translocation of Lysosomal Organelles from Cytotoxic Macrophages into the Cytoplasm of Tumor Target Cells¹

Basic Research Program, National Cancer Institute Frederick Cancer Research Center, Frederick, Maryland 21701

In this study we have recorded in detail the morphological sequence of interactions between activated macrophages and tumor target cells in vitro. The study is unique because it involves the combination of several microscopic techniques that are used sequentially to study a single cell-to-cell interaction. Many such cellular interactions were examined first by time lapse cinematography; then the effector cell was identified by specific immunofluorescence, and the areas of interaction were processed for scanning and then transmission electron microscopy.

The tumor target cells were guinea pig line 10 hepatocarcinoma cells. The effectors were peritoneal exudate cells (PEC) harvested from syngeneic strain 2 guinea pigs that had been cured of a line 10 tumor by intratumoral injection of Bacillus Calmette-Guérin. Host-target cell interactions between (a) line 10 cells and PEC from Bacillus Calmette-Guérin-tumor-cured animals, (b) line 10 cells and PEC from normal animals, and (c) syngeneic guinea pig embryo cells and PEC from Bacillus Calmette-Guérin-tumor-cured animals were studied. These comparisons demonstrate that the mechanism of tumor cell killing by activated macrophages is a nonphagocytic process. Our results suggested that the macrophage-tumor cell interaction is initiated by a recognition phase that results in extracellular release of lysosomes through macrophage exocytosis and clasmatosis. Neoplastic target cell susceptibility may be the result of an active or passive uptake of lysosomes and consequently cytolysis.

¹ Research sponsored by the National Cancer Institute under Contract N01-CO-25423 with Litton Bionetics, Inc.

² Department of Biochemistry, University of Texas Medical Branch, Galveston, Texas 77550.

Received 6/ 1/76. Accepted 8/27/76.