title: Novel anti-bacterial activities of β-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation.
abstract: Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria.
authors.affiliation: Molecular Medicine Program, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Bjoern F
authors.initials: BF
authors.lastname: Kraemer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Campbell
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schwertz
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cody
authors.forename: Zechariah
authors.initials: Z
authors.lastname: Franks
authors.forename: Neal D
authors.initials: ND
authors.lastname: Tolley
authors.forename: Walter H A
authors.initials: WH
authors.lastname: Kahr
authors.forename: Stephan
authors.initials: S
authors.lastname: Lindemann
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.forename: Christian C
authors.initials: CC
authors.lastname: Yost
authors.forename: Guy A
authors.initials: GA
authors.lastname: Zimmerman
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Weyrich
mesh_terms: D001427:Bacterial Toxins / Q000276:immunology* / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006460:Hemolysin Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D015539:Platelet Activation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology*; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; C406407:DEFB1 protein, human; D006460:Hemolysin Proteins; D012333:RNA, Messenger; D023083:beta-Defensins; C021091:staphylococcal alpha-toxin
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