Related Experiment Video
Updated: Sep 21, 2026

Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
J774 macrophages secrete antibiotics via organic anion transporters
C X Cao1, S C Silverstein, H C Neu
1Department of Physiology, Columbia University, New York, New York.
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 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.
Insights
Macrophage organic anion transporters secrete antibiotics like penicillin G and norfloxacin. This transport influences antibiotic accumulation, potentially impacting treatments for intracellular bacterial infections.
Area of Science:
- Cell Biology
- Pharmacology
- Immunology
Background:
- Macrophages play a crucial role in cellular defense and drug transport.
- Organic anion transporters (OATs) are known to mediate the efflux of various anionic compounds from cells.
- The role of OATs in antibiotic secretion by macrophages is not fully understood.
Purpose of the Study:
- To investigate the role of probenecid-inhibitable organic anion transporters in the secretion of antibiotics from J774 macrophage-like cells.
- To determine if these transporters affect the intracellular accumulation of antibiotics, such as norfloxacin.
Main Methods:
- Utilized J774 macrophage-like cells.
- Investigated the transport of anionic dyes and antibiotics (Penicillin G, norfloxacin).
- Assessed the effect of probenecid, an OAT inhibitor, on antibiotic secretion and intracellular accumulation.
Main Results:
- J774 cells express probenecid-inhibitable OATs that secrete anionic dyes.
- These OATs were found to secrete Penicillin G and norfloxacin from the cytoplasm of J774 cells.
- Probenecid significantly reduced norfloxacin secretion and increased its intracellular accumulation threefold to fourfold.
Conclusions:
- Organic anion transporters in macrophages actively secrete antibiotics like penicillin G and norfloxacin.
- This efflux mechanism contributes to the regulation of intracellular antibiotic concentrations.
- The findings suggest a potential mechanism for the limited efficacy of fluoroquinolones against intracellular pathogens in vivo.
Related Concept Videos
ABC Transporters: Importer
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Antimicrobial Proteins
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Bacterial Toxins

