dc.contributor.author |
Cockeran, Riana
|
|
dc.contributor.author |
Mutepe, Ndiafhi Daphney
|
|
dc.contributor.author |
Theron, Annette J.
|
|
dc.contributor.author |
Tintinger, Gregory Ronald
|
|
dc.contributor.author |
Steel, Helen C.
|
|
dc.contributor.author |
Stivaktas, Paraskevi Irene
|
|
dc.contributor.author |
Richards, Guy A.
|
|
dc.contributor.author |
Feldman, Charles
|
|
dc.contributor.author |
Anderson, Ronald
|
|
dc.date.accessioned |
2012-05-23T08:27:41Z |
|
dc.date.available |
2012-05-23T08:27:41Z |
|
dc.date.issued |
2012 |
|
dc.description.abstract |
OBJECTIVES: Tigecycline is the prototype of the recently introduced, intravenously administered glycylcycline
class of antibiotics, developed in response to the increasing problem of antibiotic resistance in Gram-positive
bacteria, especially Staphylococcus aureus, as well as Gram-negative bacteria and anaerobes. However, relatively
little is known about the immunomodulatory potential of tigecycline, specifically its interactions with
human neutrophils. In the current study we investigated the effects of tigecycline at therapeutically relevant
concentrations and greater (0.625–10 mg/L) on alterations in cytosolic Ca2+ concentrations, generation
of antimicrobial reactive oxygen species (ROS) and release of granule proteases [elastase, matrix metalloproteinase-
8 (MMP-8) and matrix metalloproteinase-9 (MMP-9)] by human blood neutrophils activated with
the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP; 1 mM).
METHODS: Cytosolic Ca2+ concentrations were measured using fura-2/AM-based spectrofluorimetry and radiometric
procedures, generation of ROS by oxygen consumption and myeloperoxidase-mediated auto-iodination,
and protease release by ELISA procedures.
RESULTS: Exposure of the cells to fMLP resulted in activation of the generation of ROS, as well as release of the
granule proteases, all of which were significantly increased by pre-incubation of the cells with tigecycline in a
dose-dependent manner. Tigecycline-mediated enhancement of these neutrophil functions was associated
with elevations in the concentrations of cytosolic Ca2+, which appeared to result from the Ca2+ ionophore
activity of tigecycline.
CONCLUSIONS: Tigecycline, by functioning as a Ca2+ ionophore, and independent of antimicrobial activity,
potentiates the pro-inflammatory functions of human neutrophils in vitro. |
en_US |
dc.description.sponsorship |
The South African Medical Research Council
as well as by a research grant (grant number 35733) from Wyeth
Pharmaceuticals |
en_US |
dc.description.uri |
http://jac.oxfordjournals.org/ |
en_US |
dc.identifier.citation |
Cockeran, R, Mutepe, ND, Theron, AJ, Tintinger, GR, Steel, HC, Stivaktas, PI, Richards, GA, Feldman, C & Anderson R 2012, 'Calcium-dependent potentiation of the pro-inflammatory functions of human neutrophils by tigecycline in vitro', Journal of Antimicrobial Chemotherapy, vol. 67, no. 1, pp. 130-137. |
en_US |
dc.identifier.issn |
0305-7453 (print) |
|
dc.identifier.issn |
0305-7453 (print) |
|
dc.identifier.other |
10.1093/jac/dkr441 |
|
dc.identifier.uri |
http://hdl.handle.net/2263/18833 |
|
dc.language.iso |
en |
en_US |
dc.publisher |
Oxford University Press |
en_US |
dc.rights |
© The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The definitive publisher-authenticated version Cockeran, R, Mutepe, ND, Theron, AJ, Tintinger, GR, Steel, HC, Stivaktas, PI, Richards, GA, Feldman, C & Anderson R 2012, 'Calcium-dependent potentiation of the pro-inflammatory functions of human neutrophils by tigecycline in vitro', Journal of Antimicrobial Chemotherapy, vol. 67, pp. 130-137. is available online at:http://jac.oxfordjournals.org/. |
en_US |
dc.subject |
Calcium ionophore |
en_US |
dc.subject |
Doxycycline |
en_US |
dc.subject |
Innate immunity |
en_US |
dc.subject |
Minocycline |
en_US |
dc.subject |
Oxidant scavenger |
en_US |
dc.subject |
Tetracycline |
en_US |
dc.title |
Calcium-dependent potentiation of the pro-inflammatory functions of human neutrophils by tigecycline in vitro |
en_US |
dc.type |
Postprint Article |
en_US |