Tobramycin-induced modulation of macrophage Fc-receptors.
Tobramycin is an aminoglycoside that is used therapeutically for chronic pulmonary infection that occurs in cystic fibrosis patients. The effect of this antibiotic on Fc-receptor expression was investigated using rat alveolar macrophages. When macrophage monolayers were incubated for 30 min with low concentrations of tobramycin (0.03-2.4 micrograms/ml) similar to those found in the cystic fibrosis lung, Fc-receptor expression was enhanced. This effect was dose-, temperature- and time-dependent. After 1 h pre-incubation antibody-labelled erythrocyte (EAG) binding returned to normal values and after 2 h inhibition was observed. When culture supernatants prepared from antibiotic-treated macrophages were incubated with EAG for 30 min, binding of these cells to the macrophages was decreased. This inhibition was directly proportional to the amount of supernatant added to the red cells and was greatest when the supernatant had been prepared from macrophages incubated with the antibiotic for 1 h. When macrophage monolayers were incubated for 1 h with supernatants from tobramycin-treated macrophages subsequent binding of EAG was increased. The supernatants also caused the agglutination of antibody-sensitised erythrocytes. This activity was lost after the supernatants had been absorbed against EAG. It is proposed that the supernatants contain released Fc-receptors and that tobramycin causes an increase in the shedding of Fc-receptors from the macrophage membrane. The mechanism of action of tobramycin and the in vivo relevance of these results is discussed.
Department of Bacteriology, University Medical School, Edinburgh, U.K.
A M
AM
Oliver
D M
DM
Weir
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D011961:Receptors, Fc / Q000187:drug effects / Q000378:metabolism*; D012397:Rosette Formation; D013696:Temperature; D013997:Time Factors; D014031:Tobramycin / Q000494:pharmacology*
D000936:Antigen-Antibody Complex; D011961:Receptors, Fc; D014031:Tobramycin