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The Ultrastructure of Target Cells and Immune Macrophages during Their Interaction in Vitro¹

Department of Microbiology, University of Washington, Seattle, Washington 98105

The ultrastructure of L cells and immune macrophages was studied at various intervals during their in vitro interaction, which leads to mutual cell destruction. When immune macrophages were added to a monolayer of L cells, they rapidly adhered to the L cells and the adherence persisted. Electron microscopic observations during the first 3 hours showed numerous contacts between immune macrophages and target L cells in which the plasma membrane of each cell remained intact, and no obvious degenerative changes were seen. However, slender protuberances of L cell cytoplasm extended into surface invaginations of the macrophage. Electron microscopic evidence suggested that these protuberances may be pinched off and engulfed by the macrophage. Degenerative changes were seldom observed prior to complete loss of cellular integrity. The occasional manifestations of degeneration included: disruption of polysomes and the random dispersion of ribosomes, patchy degeneration within the cytoplasm, and formation of blebs consisting of large bulbous protrusions of the cell surface.

At 5 hours and later, many cells in an advanced stage of degeneration were seen. These cells often consisted of a degenerate nucleus surrounded by swollen vesicular cytoplasmic components and little or no plasma membrane. The degeneration apparently progresses very rapidly once it has been initiated.

These ultrastructural studies, when considered in the light of other experimental data, suggest that the following sequence of events occurs during the target L cell-immune macrophage reaction in vitro. The first stage consists of the rapid and strong adherence of the immune macrophage to the target cell as the result of the reaction of the cytophilic antibody on the surface of the macrophage and the antigens of the plasma membrane of the L cell. During the second stage, the immune macrophages are exposed to the antigens of the target cell by contact and by phagocytosis of surface protuberances of the target cells. This event may provide a stimulus for the synthesis of a "mediator" for cell destruction by the macrophage, or may act directly to bring about cell destruction.

¹ Supported in part by USPHS Research Grant CA-05698 from the National Cancer Institute.

Received 5/24/68. Accepted 10/ 7/68.