Stimulation of rat peritoneal mast cells induces phagocytosis of adriamycin by rat peritoneal macrophages

Rat and beige mouse peritoneal mast cells, induced to exocytose with the antineoplastic agent adriamycin, extrude their granule remnants in the extracellular medium. These granules are loaded with the fluorescent drug adriamycin and exhibit intense yellow-reddish fluorescent staining. Granules extruded from mast cells were ultimately phagocytosed and could be observed inside the macrophages by fluorescence microscopy. All stages of the internalization process could be followed by electron microscopy. Granules adhering to the cell surface of macrophages were first embraced by short superficial projections, then enveloped by deep surface infoldings, and finally engulfed into the macrophage cytoplasm. Phagocytosis occurred exclusively in macrophages; granules were observed also on the surface of eosinophils and lymphocytes, but never inside these cells. The concentrations of adriamycin in macrophages, measured by spectrofluorimetry, were significantly higher when these cells were incubated with adriamycin and granule remnants in comparison with adriamycin alone. Preincubation with the endocytosis inhibitor cytochalasin B significantly reduced the granule mediated adriamycin uptake. As a consequence of the phagocytosis of adriamycin loaded mast cell granules, macrophages can concentrate the antineoplastic drug. These cells act as reservoirs of adriamycin and could have an important role in both the antitumor and toxic effects of the drug.