TY - JOUR
AU - Garscha, Ulrike
AB - Massive neutrophil infiltration is an early key event in infectious inflammation, accompanied by chemotactic leukotriene (LT)B generation. LTB biosynthesis is mediated by 5-lipoxygenase (5-LOX), but which pathogenic factors cause 5-LOX 4 4 activation during bacterial infections is elusive. Here, we reveal staphylococcal exotoxins as 5-LOX activators. Conditioned medium of wild-type Staphylococcus aureus but not of exotoxin-deficient strains induced 5-LOX activation in transfected HEK293 cells. Two different staphylococcal exotoxins mimicked the effects of S. aureus-conditioned medium: (1) the pore- forming toxin α-hemolysin and (2) amphipathic α-helical phenol-soluble modulin (PSM) peptides. Interestingly, in human neutrophils, 5-LOX activation was exclusively evoked by PSMs, which was prevented by the selective FPR2/ALX receptor antagonist WRW4. 5-LOX activation by PSMs was confirmed in vivo as LT formation in infected paws of mice was impaired in response to PSM-deficient S. aureus. Conclusively, exotoxins from S. aureus are potent pathogenic factors that activate 5-LOX and induce LT formation in neutrophils. Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s0001 8-019-03393 -x) contains supplementary material, which is available to authorized users. * Ulrike Garscha Lorena Tuchscherr ulrike.garscha@uni-jena.de lorena.tuchscherrdehauschopp@med.uni-jena.de Erik Romp Oliver Werz erik.romp@uni-jena.de oliver.werz@uni-jena.de Vandana Arakandy Department of Pharmaceutical/Medicinal Chemistry, vandana.arakandy@med.uni-jena.de Institute of Pharmacy, Friedrich-Schiller-University Jena, Jana Fischer Philosophenweg 
TI - Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis
JF - Cellular and Molecular Life Sciences
DO - 10.1007/s00018-019-03393-x
DA - 2019-12-05
UR - https://www.deepdyve.com/lp/springer-journals/exotoxins-from-staphylococcus-aureus-activate-5-lipoxygenase-and-N6AEEqajGj
SP - 1
EP - 18
VL - OnlineFirst
IS - 
DP - DeepDyve
ER -