antibiotic. A similar study has been performed by
Jerjomiceva et al. ( 2014 ) who tested the influ-
ence of the fluoroquinolone enrofloxacin on
bovine granulocytes. Enrofloxacin is used for
lactating cattle for treatment of mastitis induced
byStaphylococcus aureusandEscherichia coli.
The authors show that enrofloxacin induces the
formation of bovine NETs and inhibits phagocy-
tosis ofStaphylococcus aureus. In the present
study we did not notice similar effects as treat-
ment with either antibiotic used failed to induce
NETs release in resting neutrophils (Fig.1a). The
discrepancy between the results of the two stud-
ies is explicable by species differences and
by structural differences in the antibiotics.
Jerjomiceva et al. ( 2014 ) have found that
enrofloxacin-induced NETs release is mediated
by reactive oxygen species (ROS) and
citrullination of histones; the two mechanisms
that play a pivotal role in NETs formation
(Keshari et al. 2013 ; Wang et al. 2009 ). Genta-
micin is capable of increasing ROS formation
(Martinez-Salgado et al. 2002 ). However, a
ROS-linked mechanism can hardly be
involved in the interaction between neutrophils
releasing NETs and gentamicin in the present
study. If it were we would have expected an
increase, rather than decrease, in NETs release.
Moreover, the effect of gentamicin on NETs
release cannot be related to ROS formation as
gentamicin affected NETosis triggered by both
ROS-dependent (PMA) and ROS-independent
(CI) stimuli.
Schilcher et al. ( 2014 ) have shown that
clindamycin, a linkozamide antibiotic inhibiting
protein synthesis, decreases the ability ofStaph-
ylococcus aureusto degrade neutrophil extracel-
lular traps. A reduced NETs degradation is
associated with inhibited nuclease activity. That
shows that antibiotics can affect not only the
ability of phagocytic cells to release NETs, but
also modify bacteria defense systems against
human innate immunity.
NETs are beneficial as they limit the area
of inflammation and kill bacteria, but, on the
other hand, the content of NETs can be presented
to cells of the immune system and exacerbate
autoimmune diseases like systemic lupus
erythematosus. Our current results raise a nag-
ging question of the clinical meaning of the anti-
biotic influence on NETs release. It can be
suggested that it would be advisable in some
patients to choose, if only feasible, antibiotics
that are capable of increasing NETs formation
and thus enhance the antimicrobial response. In
others, suffering from NETs-related diseases, it
would be optimal to use antibiotics that diminish
NETosis.
In synopsis, we believe we have demonstrated
that antibiotics influence NETs formation in
humans. The finding is of clear therapeutic
importance in infectious diseases in patients
suffering from NET-related diseases.Acknowledgments This study was supported by a Grant
for Young Scientist no. 1WW/PM11/15/15 funded by the
Dean of the First Faculty of Medicine, Warsaw Medical
University in Warsaw, Poland.Conflicts of Interest The authors declare no conflicts of
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