Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps

Robert D Gray, Christopher Lucas, Annie Mackellar, Feng Li, Katia Hiersemenzel, Chris Haslett, Donald J Davidson, Adriano G Rossi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number12
Number of pages8
JournalJournal of inflammation
Volume10
Issue number1
DOIs
Publication statusPublished - 21 Mar 2013

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