Ultrastructure of interactions between activated murine natural killer cells and melanoma cells in an extracellular matrix (Matrigel) environment.

Abstract

Mixed suspensions of B16-F10 melanoma cells and murine interleukin 2 (IL2)-activated (adherent) natural killer (A-NK) cells cultured for 5 days were enclosed in gelled droplets of reconstituted basement membrane extracellular matrix (Matrigel). After incubation under cell culture conditions +/- IL2, samples were fixed for electron microscopy after 10 min and 2, 6, and 24 h. At the first time point cells were rounded and randomly distributed in the gel, at 2 h A-NK cells migrated vividly and formed contacts with target cells. At 6 h there were extensive effector:target conjugates and melanoma cell debris in the gel. Directed exocytosis of A-NK cell-specific granules could not be verified. At 24 h very few intact B16 cells remained in IL2-substituted specimens and there were large amounts of lytic melanoma cell remnants; in the absence of IL2 substantial numbers of surviving melanoma cells formed aggregates. At this time some A-NK cells had ingested melanoma cell components which probably fused with specific two-compartment granules to form large phagolysosomes. A-NK cells enlarged into a giant cell type with huge cytoplasmic accumulations of amorphous material described as mucoid masses by others.