title: Staphylococcus aureus α-hemolysin promotes platelet-neutrophil aggregate formation.
abstract: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe hemorrhagic necrotizing pneumonia associated with high mortality. Exotoxins have been implicated in the pathogenesis of this infection; however, the cellular mechanisms responsible remain largely undefined. Because platelet-neutrophil aggregates (PNAs) can dysregulate inflammatory responses and contribute to tissue destruction, we investigated whether exotoxins from MRSA could stimulate formation of PNAs in human whole blood. Strong PNA formation was stimulated by toxins from stationary phase but not log phase CA-MRSA, and α-hemolysin was singularly identified as the mediator of this activity. MRSA exotoxins also caused neutrophil (polymorphonuclear leukocyte) activation, as measured by increased CD11b expression, although platelet binding was not driven by this mechanism; rather, α-hemolysin-induced PNA formation was solely platelet P-selectin dependent. These findings suggest a role for S. aureus α-hemolysin-induced PNA formation in alveolar capillary destruction in hemorrhagic/necrotizing pneumonia caused by CA-MRSA and offer novel targets for intervention.
authors.affiliation: Research and Development Service, Infectious Diseases Section, Veterans Affairs Medical Center, Boise, Idaho 83702, USA. (tanyalak.parimon@va.gov
authors.forename: Tanyalak
authors.initials: T
authors.lastname: Parimon
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Devin D
authors.initials: DD
authors.lastname: Bolz
authors.forename: Eric R
authors.initials: ER
authors.lastname: McIndoo
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Bayer
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Stevens
authors.forename: Amy E
authors.initials: AE
authors.lastname: Bryant
mesh_terms: D000328:Adult; D001427:Bacterial Toxins / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion; D017714:Community-Acquired Infections / Q000382:microbiology / Q000473:pathology*; D005260:Female; D006460:Hemolysin Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000472:pathogenicity*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology*; D055815:Young Adult
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin
keywords: Staphylococcus aureus; necrotizing pneumonia; platelet-neutrophil aggregates; α-hemolysin