Effects of phagocytosis on antibiotic and nucleoside uptake by human polymorphonuclear leukocytes

Abstract

The ability of antibiotics to enter phagocytes during infection with facultative intracellular organisms was investigated using an in vitro model. Human polymorphonuclear leukocytes (PMNLs) were incubated with ingestible particles or phorbol myristate acetate (PMA), after which radiolabeled antibiotics were added to the cell suspension. Antibiotic uptake, determined by a velocity-gradient centrifugation technique, was expressed as the cellular:extracellular (C/E) antibiotic concentration ratio. Phagocytosis or PMA exposure enhanced PMNL clindamycin uptake (for example, C/E ratio of 12 for control vs 30 after zymosan). Entry of penicillin was unaffected and erythromycin uptake was slightly decreased after phagocytosis. Because clindamycin uptake by phagocytes is mediated by the nucleoside transport system, adenosine uptake after phagocytosis was studied. Adenosine uptake was stimulated by phagocytosis, and this increase was inhibited by clindamycin. Thus, clindamycin uptake, mediated by the nucleoside transport system, was augmented by phagocytosis. This marked stimulation of a membrane transport system by phagocytosis has not been previously described.