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Published on: January 6, 2014
Uptake, transport, and delivery of antimicrobial agents by human polymorphonuclear neutrophils
1Division of Infectious Diseases, University of Virginia Health System, Charlottesville, Virginia 22908-1341, USA. gm@virginia.edu
Abstract:
Polymorphonuclear neutrophils (PMN) are attracted to sites of infection. They have the potential to deliver antimicrobial agents to these sites if the agents enter the cells and do not alter migration. Penicillin G did not enter cells and was not transported by PMN. We found that azithromycin, ciprofloxacin, levofloxacin, moxifloxacin, and telithromycin were concentrated in PMN and transported toward a chemoattractant. These antimicrobial agents were released from the PMN and inhibited the growth of bacteria on test plates.
Insights
Certain antibiotics, including azithromycin and fluoroquinolones, are concentrated and transported by polymorphonuclear neutrophils (PMN). These PMN-delivered antibiotics effectively inhibit bacterial growth at infection sites.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Polymorphonuclear neutrophils (PMN) migrate to infection sites.
- Antimicrobial agents need to enter and be transported by PMN without altering migration to be effective.
- Penicillin G was found to be ineffective as it did not enter or get transported by PMN.
Purpose of the Study:
- To investigate the cellular uptake, transport, and release of specific antibiotics by PMN.
- To determine if certain antibiotics can be effectively delivered to infection sites via PMN.
Main Methods:
- PMN were exposed to various antibiotics.
- Antibiotic concentration within PMN was measured.
- PMN migration towards a chemoattractant in the presence of antibiotics was assessed.
- Antibiotic release from PMN and subsequent bacterial growth inhibition were evaluated.
Main Results:
- Azithromycin, ciprofloxacin, levofloxacin, moxifloxacin, and telithromycin were concentrated within PMN.
- These antibiotics were transported by PMN towards a chemoattractant.
- The antibiotics were released from PMN and demonstrated inhibitory effects on bacterial growth.
Conclusions:
- Several key antibiotics are effectively internalized, transported, and released by PMN.
- PMN can serve as a delivery mechanism for these antimicrobial agents to infection sites.
- This mechanism holds potential for enhancing antimicrobial efficacy in treating infections.
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