Cao C X, Silverstein S C, Neu H C, Steinberg T H
Department of Physiology, Columbia University, New York, New York.
J Infect Dis. 1992 Feb;165(2):322-8. doi: 10.1093/infdis/165.2.322.
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 norfloxacin enters macrophages readily. Probenecid retarded the secretion of intracellular norfloxacin by J774 cells and enhanced norfloxacin accumulation three- to fourfold. Thus the intracellular accumulation of norfloxacin is regulated in part by organic anion transporters that secrete norfloxacin (and penicillin G) from J774 cells. This transport process may have clinical significance, as fluoroquinolones inhibit growth of intracellular pathogens such as mycobacteria and Brucella organisms in vitro but fail to arrest infections with these organisms in vivo.
小鼠巨噬细胞和J774巨噬样细胞表达丙磺舒可抑制的有机阴离子转运体，这些转运体可将阴离子染料从细胞胞质基质中移除，并将这些染料分泌到细胞外介质中。目前的研究表明，这些转运体还能从J774巨噬细胞中分泌抗生素。青霉素G透过J774细胞的能力较差，但在被导入细胞胞质后，它会以丙磺舒可抑制的方式分泌。喹诺酮类药物诺氟沙星很容易进入巨噬细胞。丙磺舒抑制了J774细胞对细胞内诺氟沙星的分泌，并使诺氟沙星的积累增加了三到四倍。因此，诺氟沙星在细胞内的积累部分受有机阴离子转运体的调节，这些转运体可从J774细胞中分泌诺氟沙星（和青霉素G）。这一转运过程可能具有临床意义，因为氟喹诺酮类药物在体外可抑制细胞内病原体如分枝杆菌和布鲁氏菌的生长，但在体内却无法阻止这些病原体的感染。
