TY - JOUR
T1 - Glycopeptide Antibiotics Impair Neutrophil Effector Functions
AU - Ettel, Paul
AU - Sehgal, Al Nasar Ahmed
AU - Harrison, Nicole
AU - Pickl, Winfried F
AU - Grabmeier-Pfistershammer, Katharina
N1 - Funding Information:
This work was supported by the Medical University of Vienna and the Danube Allergy Research Cluster (Danube ARC) supported by the State of Lower Austria.
Publisher Copyright:
© 2023 The Author(s). Published by S. Karger AG, Basel. This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.
PY - 2023/6/15
Y1 - 2023/6/15
N2 - INTRODUCTION: Neutrophilic granulocytes represent the first line of defense against microorganisms. Granulocytes phagocytose microorganisms and specifically synthesize oxygen radicals against them, which eventually kills the invaders.METHODS: Neutrophilic granulocytes were isolated from peripheral blood of healthy volunteer donors. Putative interference of new-generation antibiotics with neutrophil function was tested using a collection of granulocyte-stimulating agents and Amplex™ Red-based plate assay and flow cytometry-based respiratory burst assays. In addition, phagocytosis of E. coli, IL-8 production, bactericidal activity, and CD62L expression of granulocytes were evaluated.RESULTS: Of note, we found that the two glycopeptide antibiotics dalbavancin and teicoplanin inhibited ROS production upon granulocyte activation via different signaling pathways in a dose-dependent manner. Dalbavancin also blocked the PMA-induced shedding of CD62L. In contrast, the oxazolidinone antibiotics tedizolid and linezolid had no effect on neutrophil function, while the combination of ceftazidime/avibactam dose dependently inhibited the fMLP/Cytochalasin B-induced granulocyte burst in a dose-dependent manner. Additionally, we showed that dalbavancin and teicoplanin as well as sulfametrole/trimethoprim and ceftazidime/avibactam inhibited baseline and PMA-induced IL-8 production by neutrophilic granulocytes. Moreover, dalbavancin impaired the bactericidal activity of neutrophilic granulocytes.CONCLUSION: We here identified hitherto unknown inhibitory effects of several classes of antibiotics on the effector functions of neutrophilic granulocytes.
AB - INTRODUCTION: Neutrophilic granulocytes represent the first line of defense against microorganisms. Granulocytes phagocytose microorganisms and specifically synthesize oxygen radicals against them, which eventually kills the invaders.METHODS: Neutrophilic granulocytes were isolated from peripheral blood of healthy volunteer donors. Putative interference of new-generation antibiotics with neutrophil function was tested using a collection of granulocyte-stimulating agents and Amplex™ Red-based plate assay and flow cytometry-based respiratory burst assays. In addition, phagocytosis of E. coli, IL-8 production, bactericidal activity, and CD62L expression of granulocytes were evaluated.RESULTS: Of note, we found that the two glycopeptide antibiotics dalbavancin and teicoplanin inhibited ROS production upon granulocyte activation via different signaling pathways in a dose-dependent manner. Dalbavancin also blocked the PMA-induced shedding of CD62L. In contrast, the oxazolidinone antibiotics tedizolid and linezolid had no effect on neutrophil function, while the combination of ceftazidime/avibactam dose dependently inhibited the fMLP/Cytochalasin B-induced granulocyte burst in a dose-dependent manner. Additionally, we showed that dalbavancin and teicoplanin as well as sulfametrole/trimethoprim and ceftazidime/avibactam inhibited baseline and PMA-induced IL-8 production by neutrophilic granulocytes. Moreover, dalbavancin impaired the bactericidal activity of neutrophilic granulocytes.CONCLUSION: We here identified hitherto unknown inhibitory effects of several classes of antibiotics on the effector functions of neutrophilic granulocytes.
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U2 - 10.1159/000530865
DO - 10.1159/000530865
M3 - Journal article
C2 - 37321197
SN - 1018-2438
SP - 1
EP - 17
JO - International Archives of Allergy and Immunology
JF - International Archives of Allergy and Immunology
ER -