Characteristics and mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes

Hand, W. Lee; Hand, D L

doi:10.1016/s0924-8579(01)00430-7

Cited by 68 publications

(59 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, various in vitro accumulation and release studies of macrolides have been performed. The cells preferentially analyzed in those experiments were phagocytes, in particular, human polymorphonuclear neutrophils (PMNs) (11,13,20,36). Based on the results obtained, Labro (17) has proposed classification of these antibiotics into two groups.…”

mentioning

confidence: 99%

“…Factors include dependence of the uptake on cell viability, temperature, pH, and extracellular Ca 2ϩ ; competition among macrolides for entry into cells; and interindividual variability in the kinetics of uptake (22,23,34,36). At the same time, considerably fewer data on the release mechanisms of macrolides from the host cells are available (11,34,36). To overcome the differences in the kinetics of uptake and efflux that have been observed as a result of interindividual variability among PMNs from different donors, studies of various phagocytic and nonphagocytic cell lines have begun (1,2,4,22,28,29,35).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cellular Uptake and Efflux of Azithromycin, Erythromycin, Clarithromycin, Telithromycin, and Cethromycin

Bosnar

Kelnerić

Munić

et al. 2005

Antimicrob Agents Chemother

141

View full text Add to dashboard Cite

Macrolide antibiotics have an outstanding ability to concentrate within host cells, particularly phagocytes. In the study described in this paper five different macrolide antibiotics were compared regarding the uptake and release kinetics in human peripheral blood polymorphonuclear neutrophils (PMNs) and three different cell lines, two phagocytic cell lines (RAW 264.7 and THP-1) and an epithelial cell line (MDCK). Based on the results obtained, the substances tested could be clustered into different groups. Azithromycin constituted the first group, characterized by rapid and nonsaturable uptake into phagocytic cells and a high degree of retention in the preloaded cells. The second group included erythromycin and clarithromycin. These two substances do not exhibit cell specificity; consequently, they are taken up to a similar extent and are released by all cell types studied. Ketolides constituted the last group. Their uptake was saturable in cells of monocytic lineage as well as in nondifferentiated cells of myeloid lineage, and they were rapidly released from all the cell lines studied. However, in PMNs, ketolide uptake was not saturable; and unlike telithromycin, cethromycin rapidly egressed from the loaded cells.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Cellular Uptake and Efflux of Azithromycin, Erythromycin, Clarithromycin, Telithromycin, and Cethromycin

Bosnar

Kelnerić

Munić

et al. 2005

Antimicrob Agents Chemother

141

View full text Add to dashboard Cite

show abstract

“…The ability of these drugs to penetrate cells may be important in fighting obligate intracellular pathogens (2). AZM was found to have a particularly long tissue half-life, estimated at greater than 2 days in mammalian phagocytic cells, and AZM accumulation was more than 20-fold higher than ERY accumulation in human polymorphonuclear neutrophils (9). With respect to the eye, a recent study described AZM reaching high concentrations in the human conjunctiva and persisting in the cornea for at least 7 days after treatment, with a half-life of 65.7 h (18).…”

Section: Discussionmentioning

confidence: 99%

A Novel Cell-Associated Protection Assay Demonstrates the Ability of Certain Antibiotics To Protect Ocular Surface Cell Lines from Subsequent Clinical Staphylococcus aureus Challenge

Wingard

Romanowski

Kowalski

et al. 2011

Antimicrob Agents Chemother

View full text Add to dashboard Cite

In vivo effectiveness of topical antibiotics may depend on their ability to associate with epithelial cells to provide continued protection, but this contribution is not measured by standard antibiotic susceptibility tests. We report a new in vitro method that measures the ability of test antibiotics azithromycin (AZM), erythromycin (ERY), tetracycline (TET), and bacitracin (BAC) to associate with mammalian cells and to protect these cells from destruction by bacteria. Mammalian cell lines were grown to confluence using antibiotic-free medium and then incubated in medium containing a single antibiotic (0 to 512 g/ml). After incubation, the cells were challenged with Staphylococcus aureus ocular isolates, without antibiotics added to the culture medium. Epithelial cell layer integrity was assessed by gentian violet staining, and the minimum cell layer protective concentration (MCPC) of an antibiotic sufficient to protect the mammalian cells from S. aureus was determined. Staining was also quantified and analyzed. Bacterial viability was determined by culture turbidity and growth on agar plates. Preincubation of Chang and human corneal limbal epithelial cells with AZM, ERY, and TET at >64 g/ml provided protection against AZM-susceptible S. aureus strains, with increasing protection at higher concentrations. TET toxicity was demonstrated at >64 g/ml, whereas AZM displayed toxicity to one cell line at 512 g/ml. BAC failed to show consistent protection at any dose, despite bacterial susceptibility to BAC as determined by traditional antibiotic susceptibility testing. A range of antibiotic effectiveness was displayed in this cell association assay, providing data that may be considered in addition to traditional testing when determining therapeutic dosing regimens.

show abstract

“…74 This rapid response to inflammatory signals has led to the proposed use of neutrophils as vehicles for delivering therapeutics to sites of infection or injury. 75 However, transplanted cells do not always localize to the sites of interest. Suratt et al 76 characterized inactive and activated neutrophil populations after transplant.…”

Section: Circulating Cell Types Are Ideal For Biological Targeting Stmentioning

confidence: 99%

Cell vehicle targeting strategies

2008

View full text Add to dashboard Cite

Use of cells as therapeutic carriers has increased in the past few years and has developed as a distinct concept and delivery method. Cell-based vehicles are particularly attractive for delivery of biotherapeutic agents that are difficult to synthesize, have reduced half-lives, limited tissue penetrance or are rapidly inactivated upon direct in vivo introduction. Initial studies using cell-based approaches served to identify some of the key factors for the success of this type of therapeutic delivery. These factors include the efficiency of cell loading with a therapeutic payload, the means of cell loading and the nature of therapeutics that cells can carry. However, one important aspect of cell-based delivery yet to be fully investigated is the process of actual delivery of the cell payload in vivo. In this regard, the potential ability of cell carriers to provide site-specific or targeted delivery of therapeutics deserves special attention. The present review focuses on a variety of targeting approaches that may be utilized to improve cell-based therapeutic delivery strategies. The different aspects of targeting that can be applied to cell vehicles will be discussed, including physical methods for directing cell distribution, intrinsic cell-mediated homing mechanisms and the feasibility of engineering cells with novel targeting mechanisms. Development of cell targeting strategies will further advance cell vehicle applications, broaden the applicability of this delivery approach and potentiate therapeutic outcomes.

show abstract

Characteristics and mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes

Cited by 68 publications

References 38 publications

Cellular Uptake and Efflux of Azithromycin, Erythromycin, Clarithromycin, Telithromycin, and Cethromycin

Cellular Uptake and Efflux of Azithromycin, Erythromycin, Clarithromycin, Telithromycin, and Cethromycin

A Novel Cell-Associated Protection Assay Demonstrates the Ability of Certain Antibiotics To Protect Ocular Surface Cell Lines from Subsequent Clinical Staphylococcus aureus Challenge

Cell vehicle targeting strategies

Contact Info

Product

Resources

About