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American Journal of Pathology, Vol 112, 101-111, Copyright © 1983 by American Society for Investigative Pathology

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Ultrastructural studies of the interaction between liposome-activated human blood monocytes and allogeneic tumor cells in vitro

CD Bucana, LC Hoyer, AJ Schroit, E Kleinerman and IJ Fidler

Human blood monocytes were activated to become tumoricidal by incubation with liposomes containing muramyl tripeptide- phosphatidylethanolamine, a lipophilic derivative of muramyl dipeptide. The interaction of both tumoricidal and control monocytes with target melanoma cells was analyzed by means of light microscopy and scanning and transmission electron microscopy. The authors found increased clustering around the melanoma cells by tumoricidal monocytes as compared with the control monocytes. The initial clustering of the tumoricidal monocytes around the tumor cells was followed by the establishment of numerous focal points of contact (binding), some of which actually exhibited areas of discontinuous membrane, a finding confirmed by stereophotography. By 24-48 hours of cocultivation, many of the target cells exhibited zones of vacuolation in the immediate vicinity of the tumoricidal monocytes, suggesting target cell damage. (This finding was confirmed by time-course cytotoxicity assays.) The authors conclude that tumor cell lysis mediated by activated human blood monocytes occurs as the final step in a process that includes the establishment of a direct cell-cell contact, damage to the target cell membrane, and the development of areas of vacuolation in the target cells.

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