Binding of aminoglycoside antibiotics by degranulating mast cells.
The aminoglycoside antibiotics are polycationic at physiological pH and hence do not enter most cells. Indeed, when intact mast cells were incubated with gentamicin or tobramycin, extremely low concentrations of the two drugs could be measured. In contrast, when a controlled, specific degranulation of mast cells was induced by treating the cells with compound 48/80, Adriamycin or concanavalin A, a dose-dependent histamine release was observed and a significant increase of the intracellular concentrations of the aminoglycosides resulted. The uptake of gentamicin and tobramycin was not dependent on the type of stimulus, but was proportional to the quantity of histamine release. The aminoglycoside binding to granular material obtained from sonicated cells was similar to that of degranulating mast cells. These data suggest the occurrence of ionic interactions between the positively charged groups of the aminoglycosides and the negatively charged groups of granular matrix that are exposed as a consequence of exocytosis. The significant of this phenomenon is at present unclear but studies are in progress to clarify the fate of the aminoglycosides bound to mast cells.
Decorti
G
G
Department of Biomedical Sciences, Faculty of Medicine, Trieste, Italy.
Candussio
L
L
Klugmann
F B
FB
Baldini
L
L
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D015550:Cell Degranulation; D003594:Cytoplasmic Granules / Q000378:metabolism; D004317:Doxorubicin; D005839:Gentamicins / Q000378:metabolism; D006636:Histamine Release; D008407:Mast Cells / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D014031:Tobramycin / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D004317:Doxorubicin; D014031:Tobramycin