Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis.
Cell Mol Life Sci
; 77(19): 3841-3858, 2020 Oct.
Article
in En
| MEDLINE
| ID: mdl-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Staphylococcus aureus
/
Arachidonate 5-Lipoxygenase
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Leukotrienes
/
Enzyme Activation
/
Exotoxins
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Mol Life Sci
Year:
2020
Document type:
Article