title: Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps.
abstract: BACKGROUND
  Activation of NADPH oxidase is required for neutrophil extracellular trap (NET) formation. Protein kinase C (PKC) is an upstream mediator of NADPH oxidase activation and thus likely to have a role in NET formation.
  
  
  METHODS
  Pharmacological inhibitors were used to block PKC activity in neutrophils harvested from healthy donor blood.
  
  
  RESULTS
  Pan PKC inhibition with Ro-31-8220 (p<0.001), conventional PKC inhibition with Go 6976 (p<0.001) and specific PKCβ inhibition with LY333531 (p<0.01) blocked NET formation in response to PMA. Inhibition of novel and atypical PKC had no effect. LY333531 blocked NET induction by the diacylglycerol analogue OAG (conventional PKC activator) (p<0.001).
  
  
  CONCLUSIONS
  Conventional PKCs have a prominent role in NET formation. Furthermore PKCβ is the major isoform implicated in NET formation.
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gray
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lucas
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK.
authors.forename: Annie
authors.initials: A
authors.lastname: MacKellar
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK.
authors.forename: Katia
authors.initials: K
authors.lastname: Hiersemenzel
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Haslett
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, 47 Little France Crescent, Edinburgh, Scotland, UK.
authors.forename: Adriano G
authors.initials: AG
authors.lastname: Rossi