ArticleAntimicrobial agents and chemotherapy1997
Cellular accumulation of the new ketolide RU 64004 by human neutrophils: comparison with that of azithromycin and roxithromycin.
Article in Antimicrobial agents and chemotherapy, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Neutrophil-mediated delivery of the combination of colistin and azithromycin for the treatment of bacterial infection.iScience · 2022Article
- Antibiotics in malaria therapy: which antibiotics except tetracyclines and macrolides may be used against malaria?Malaria journal · 2016Review
- Ketolide agents HMR 3004 and HMR 3647 (telithromycin) inhibit the growth of Plasmodium falciparum in vitro.African health sciences · 2015Article
- Azithromycin inhibits IL-1 secretion and non-canonical inflammasome activation.Scientific reports · 2015Article
- Azithromycin enhances phagocytic killing of Aggregatibacter actinomycetemcomitans Y4 by human neutrophils.Journal of periodontology · 2015Article
- Ketolides--the modern relatives of macrolides : the pharmacokinetic perspective.Clinical pharmacokinetics · 2009Review
- Cellular uptake and efflux of azithromycin, erythromycin, clarithromycin, telithromycin, and cethromycin.Antimicrobial agents and chemotherapy · 2005Article
- Interaction of the new ketolide ABT-773 (cethromycin) with human polymorphonuclear neutrophils and the phagocytic cell line PLB-985 in vitro.Antimicrobial agents and chemotherapy · 2004Article
- Effect of telithromycin (HMR 3647) on polymorphonuclear neutrophil killing of Staphylococcus aureus in comparison with roxithromycin.Antimicrobial agents and chemotherapy · 2002Article
- The ketolides: a critical review.Drugs · 2002Review
- Cellular uptake of two fluoroketolides, HMR 3562 and HMR 3787, by human polymorphonuclear neutrophils in vitro.Antimicrobial agents and chemotherapy · 2001Article
- Telithromycin is active against Mycobacterium avium in mice despite lacking significant activity in standard in vitro and macrophage assays and is associated with low frequency of resistance during treatment.Antimicrobial agents and chemotherapy · 2001Article
- In vitro pharmacodynamic studies of activities of ketolides HMR 3647 (Telithromycin) and HMR 3004 against extracellular or intracellular Helicobacter pylori.Antimicrobial agents and chemotherapy · 2001Article
- Review
- Interference of antibacterial agents with phagocyte functions: immunomodulation or "immuno-fairy tales"?Clinical microbiology reviews · 2000Review
- In vitro activities of the ketolides telithromycin (HMR 3647) and HMR 3004 compared to those of clarithromycin against slowly growing mycobacteria at pHs 6.8 and 7.4.Antimicrobial agents and chemotherapy · 2000Article
- In vitro pharmacodynamics of the new ketolides HMR 3004 and HMR 3647 (Telithromycin) against Chlamydia pneumoniae.Antimicrobial agents and chemotherapy · 2000Article
- Interactions of ofloxacin and erythromycin with the multidrug resistance protein (MRP) in MRP-overexpressing human leukemia cells.Antimicrobial agents and chemotherapy · 2000Article
- Effect of proinflammatory cytokines on the interplay between roxithromycin, HMR 3647, or HMR 3004 and human polymorphonuclear neutrophils.Antimicrobial agents and chemotherapy · 2000Article
- The new ketolide HMR3647 accumulates in the azurophil granules of human polymorphonuclear cells.Antimicrobial agents and chemotherapy · 1999Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We analyzed the uptake of RU 64004 by human neutrophils (polymorphonuclear leukocytes [PMNs]) relative to those of azithromycin and roxithromycin. RU 64004 was strongly and rapidly accumulated by PMNs, with a cellular concentration/extracellular concentration ratio (C/E) of greater than 200 in the first 5 min, and this was followed by a plateau at 120 to 180 min, with a C/E of 461 +/- 14.8 (10 experiments) at 180 min. RU 64004 uptake was moderately sensitive to external pH, and activation energy was also moderate (63 +/- 3.8 kJ/mol). RU 64004 was mainly located in PMN granules (about 70%) and egressed slowly from loaded cells, owing to avid reuptake. The possibility that PMN uptake of RU 64004 and other macrolides occurs through a carrier-mediated system was suggested by three key results. First, there existed a strong interindividual variability in uptake kinetics, suggesting variability in the numbers or activity of a transport protein. Second, macrolide uptake displayed saturation kinetics characteristic of that of a carrier-mediated transport system: RU 64004 had the highest Vmax value (3,846 ng/2.5 x 10(6) PMNs/5 min) and the lowest Km value (about 28 microM), indicating a high affinity for the transporter. Third, as observed previously with other erythromycin A derivatives, Ni2+ (a blocker of the Na+/Ca2+ exchanger which mediates Ca2+ influx in resting neutrophils) impaired RU 64004 uptake by PMNs, with a 50% inhibitory concentration of about 3.5 mM. In addition, we found that an active process is also involved in macrolide efflux, because verapamil significantly potentiated the release of all three macrolides tested. This effect of verapamil does not seem to be related to an inhibition of Ca2+ influx, because neither EGTA [ethylene glycol-bis (beta-aminoethyl ether)-N,N',N'-tetraacetic acid] nor Ni2+ modified macrolide efflux. The nature and characteristics of the entry- and efflux-mediating carrier systems are under investigation.
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