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Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis.

Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis.

Authors :
Romp, Erik
Arakandy, Vandana
Fischer, Jana
Wolz, Christiane
Siegmund, Anke
Löffler, Bettina
Tuchscherr, Lorena
Werz, Oliver
Garscha, Ulrike
Source :
Cellular & Molecular Life Sciences. Oct2020, Vol. 77 Issue 19, p3841-3858. 18p.
Publication Year :
2020

Abstract

Massive neutrophil infiltration is an early key event in infectious inflammation, accompanied by chemotactic leukotriene (LT)B4 generation. LTB4 biosynthesis is mediated by 5-lipoxygenase (5-LOX), but which pathogenic factors cause 5-LOX 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1420682X
Volume :
77
Issue :
19
Database :
Academic Search Index
Journal :
Cellular & Molecular Life Sciences
Publication Type :
Academic Journal
Accession number :
146008118
Full Text :
https://doi.org/10.1007/s00018-019-03393-x