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.

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.

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