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- Title
Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps.
- Authors
Gray, Robert D.; Lucas, Christopher D.; MacKellar, Annie; Feng Li; Hiersemenzel, Katia; Haslett, Chris; Davidson, Donald J.; Rossi, Adriano G.
- 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.
- Subjects
PROTEIN kinase C; NADPH oxidase; NEUTROPHILS; BLOOD donors; DIGLYCERIDES
- Publication
Journal of Inflammation, 2013, Vol 10, Issue 1, p1
- ISSN
1476-9255
- Publication type
Article
- DOI
10.1186/1476-9255-10-12