Differential effects of clindamycin on neutrophils of healthy donors and septic patients

Wittmann, Sigrid; Arlt, Matthias; Rothe, Gregor; Fröhlich, D.

doi:10.1016/j.intimp.2004.04.003

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…In our study, neutrophils that were preincubated with clindamycin showed higher intake of fluorescein-conjugated Escherichia coli . This is in line with previous reports describing the influence of lincosamides on granulocyte functions [ 14 , 15 ]. However, we did not find any influence on NET formation in vitro after stimulation with PMA.…”

Section: Discussionsupporting

confidence: 93%

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The effect of clindamycin and amoxicillin on neutrophil extracellular trap (NET) release

Bystrzycka

Moskalik

Sieczkowska

et al. 2016

cejoi

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Neutrophil extracellular traps (NETs) are threads of nuclear DNA complexed with antimicrobial proteins released by neutrophils to extracellular matrix to bind, immobilise, and kill different pathogens. NET formation is triggered by different physiological and non-physiological stimulants. It is also suggested that antibiotics could be non-physiological compounds that influence NET release.The aim of the study was to investigate the effect of clindamycin and amoxicillin on NET release and the phagocyte function of neutrophils.Neutrophils isolated from healthy donors by density centrifugation method were incubated with amoxicillin or clindamycin for two hours, and then NET release was stimulated with phorbol 12-myristate 13-acetate (PMA). After three hours of incubation with PMA NETs were quantified as amount of extracellular DNA by fluorometry and visualised by immunofluorescent microscopy. The percent of phagocyting cells was measured by flow cytometry.We showed that amoxicillin induces NET formation (increase of extracellular DNA fluorescence, p = 0.03), while clindamycin had no influence on NET release (p > 0.05), as confirmed by quantitative measurement and fluorescent microscopy. Regarding phagocyte function, both antibiotics increased bacterial uptake (43.3% and 61.6% median increase for amoxicillin and clindamycin, respectively).We concluded that the ability of antibiotics to modulate NET release depends on the antibiotic used and is not associated with their ability to influence phagocytosis.

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Section: Discussionsupporting

confidence: 93%

“…Moreover, clindamycin increases oxidative burst of neutrophils [ 13 ]. In several studies clindamycin showed a positive effect on phagocytosis [ 7 , 14 , 15 ]. Amoxicillin belongs to the β-lactam antibiotics, and its action is based on inhibition of the synthesis of bacterial cell wall.…”

Section: Introductionmentioning

confidence: 99%

The effect of clindamycin and amoxicillin on neutrophil extracellular trap (NET) release

Bystrzycka

Moskalik

Sieczkowska

et al. 2016

cejoi

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The drug designer´s guide to selectivity

Gottfries

2006

Chemometrics and Intelligent Laboratory Systems

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Polymorphonuclear Leukocyte Dysfunction Syndrome in Patients With Increasing Sepsis Severity

Kaufmann

Hoelzl²,

Schliephake³

et al. 2006

Shock

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Production of oxygen radicals is required for both microbicidal and tissue-toxic effector functions of granulocytes. Inasmuch as an ambivalent role of polymorphonuclear leukocytes (PMNs) may become apparent during sepsis, we studied levels of hydrogen peroxide (H2O2) production by PMNs depending upon the nature of different particulate and soluble stimuli in patients with increasing sepsis severity. Patients with sepsis (n = 15), severe sepsis (n = 12), or septic shock (n = 33) were prospectively enrolled in the study. Healthy volunteers of comparable age and sex served as controls (n = 50). Unopsonized and opsonized zymosan particles were used to assess adhesion, phagocytosis, and the associated H2O2 production. Zymosan particles are rich in beta-glucans and lectin structures that are known to trigger H2O2 production via two major non-toll-like receptor pathogen recognition receptors, comprising the lectin-binding site in the alpha-chain (CD11b) of the complement receptor type 3 and the more recently identified nonclassical C-type lectin, dectin-1. To determine H2O2 production upon cell activation by soluble stimuli, PMNs were activated by the chemotactic tripeptide (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) alone or after priming of cells by preincubation with tumor necrosis factor alpha. To get insight into the changes of fMLP receptor classical intracellular signaling pathways, PMNs were also incubated with the calcium ionophore A23187 and the phorbol ester phorbol myristate acetate, bypassing receptor-dependent signal transduction to directly activate calcium/calmodulin kinase- and protein kinase C-dependent pathways, respectively. As compared with healthy volunteers, levels of H2O2 production by PMNs from septic patients varied depending upon the nature of the activating signal: reduced (zymosan), unchanged (phorbol myristate acetate, opsonized zymosan), and enhanced (spontaneous, fMLP, fMLP + tumor necrosis factor alpha, A23187), with the changes most pronounced in patients with septic shock. Specifically, phagocytosis of zymosan and the associated H2O2 production were significantly decreased whereas spontaneous and stimulated H2O2 production elicited by soluble stimuli strongly increased. Thus, these findings suggest the development of a PMN dysfunction syndrome in patients with increasing sepsis severity. Moreover, as binding of zymosan particles to the PMNs' surface remained unchanged despite increasingly suppressed phagocytosis and associated H2O2 production, observed effects are likely to reflect defects in signaling by the lectin-binding site of CD11b and/or the beta-glucan receptor dectin-1, respectively.

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Differential effects of clindamycin on neutrophils of healthy donors and septic patients

Cited by 3 publications

References 30 publications

The effect of clindamycin and amoxicillin on neutrophil extracellular trap (NET) release

The effect of clindamycin and amoxicillin on neutrophil extracellular trap (NET) release

The drug designer´s guide to selectivity

Polymorphonuclear Leukocyte Dysfunction Syndrome in Patients With Increasing Sepsis Severity

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