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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

Erik Romp, Vandana Arakandy, Jana Fischer, Christiane Wolz, Anke Siegmund, Bettina Löffler, Lorena Tuchscherr, Oliver Werz, Ulrike Garscha

Cell Mol Life Sci. 2019 Dec 5.

PMID: 31807813

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP94716946	α-Hemolysin from Staphylococcus aureus		94716-94-6	Price

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