J774 Macrophages Secrete Antibiotics via Organic Anion Transporters

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Abstract
Mouse macrophages and J774 macrophage-like cells express probenecid-inhibitable organic anion transporters that remove anionic dyes from the cells' cytoplasmic matrix and secrete these dyes into the extracellular medium. The present studies show that these transporters also secrete antibiotics from J774 macrophages. Penicillin G permeates J774 cells poorly, but after it was introduced into the cell cytoplasm, it was secreted in a probenecid-inhibitable fashion. The quinolone norftoxacin enters macrophages readily. Probenecid retarded the secretion of intracellular norftoxacin by J774 cells and enhanced norftoxacin accumulation three- to fourfold. Thus the intracellular accumulation of norftoxacin is regulated in part by organic anion transporters that secrete norftoxacin (and penicillin G) from J774 cells. This transport process may have clinical significance, as fiuoroquinolones inhibit growth of intracellular pathogens such as mycobacteria and Brucella organisms in vitro but fail to arrest infections with these organisms in vivo.

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