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Ciprofloxacin transport by chemoattractant-activated polymorphonuclear leukocytes: regulation by priming and protein

John D Walters1, Robin J Nakkula

  • 1Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, Ohio 43218-2357, USA. walters.2@osu.edu

Antimicrobial Agents and Chemotherapy
|September 25, 2003
PubMed

Insights

Priming polymorphonuclear leukocytes (PMNs) with GM-CSF or LPS enhances their ciprofloxacin transport when activated by formyl peptides, a process mediated by protein kinase C.

Area of Science:

  • Immunology
  • Pharmacology
  • Cell Biology

Background:

  • Polymorphonuclear leukocytes (PMNs) are crucial immune cells at infection sites.
  • PMN function is modulated by priming agents like granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS), and activation signals such as formyl peptides.
  • Understanding PMN drug transport mechanisms is vital for effective antimicrobial therapy.

Purpose of the Study:

  • To investigate the effects of priming and activation on ciprofloxacin transport in PMNs.
  • To elucidate the role of protein kinase C in modulating PMN ciprofloxacin uptake.
  • To determine if priming enhances the activation-induced changes in ciprofloxacin transport.

Main Methods:

  • PMNs were treated with GM-CSF or LPS (priming) followed by formyl-Met-Leu-Phe (fMLP) activation.
  • Ciprofloxacin transport kinetics (Km) and accumulation were measured.
  • The involvement of protein kinase C was assessed.

Main Results:

  • GM-CSF or LPS alone did not significantly alter PMN ciprofloxacin transport.
  • fMLP activation alone decreased the Km and increased ciprofloxacin accumulation via protein kinase C.
  • Priming PMNs with GM-CSF or LPS dramatically potentiated the fMLP-induced enhancement of ciprofloxacin transport.

Conclusions:

  • PMN priming potentiates activation-dependent alterations in ciprofloxacin transport.
  • Protein kinase C is a key mediator in fMLP-induced changes to ciprofloxacin uptake.
  • These findings suggest novel strategies for enhancing antibiotic delivery to infection sites via PMN modulation.

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