Uptake of h-dihydrostreptomycin by macrophages in culture.

Mouse peritoneal macrophages, in culture, concentrate significant amounts of (3)H-dihydrostreptomycin, provided that the incubation period is sufficiently extended. Macrophages cultured in vitro from both stimulated and unstimulated animals concentrate the antibiotic from growth or maintenance media. The increase in cell-associated radioactivity is linear for almost a week before a plateau is reached. Calculations based on intracellular volumes of the cells indicate that the intracellular concentration of dihydrostreptomycin may attain levels greater than five times that of the external milieu. No uptake is measurable at 4 C, suggesting an active mechanism of transport into the cell. Phagocytosis of killed bacteria during incubation did not increase uptake of the antibiotic nor did the addition of poly-l-ornithine to the medium augment uptake. A nonphagocytic cell line (BHK-21) concentrated (3)H-dihydrostreptomycin to a lesser extent than the macrophages. These observations suggest that a wide variety of mammalian cells may be permeable to the antibiotic, and thus potential bactericidal action on intracellular bacteria cannot be ignored.