Protein kinase C isoforms mediate the formation of neutrophil extracellular traps

Neutrophils release extracellular traps (NETs) in response to numerous pathogenic microbes as the last suicidal resource (NETosis) in the fight against infection. Apart from the host defense function, NETs play an essential role in the pathogenesis of various autoimmune, inflammatory and malignant diseases. Therefore, understanding the molecular mechanisms of NETosis is important for regulating the aberrant or excessive NET release. Protein kinase C (PKC) is a serine/threonine kinase which is involved in various neutrophil functions, however, little is known about its implication in NETosis activated by various physiological and pharmacological stimuli. Since there are conventional, novel and atypical PKC isoforms (alpha, fiI, fiII, 8, and zeta) found in human neutrophils, we investigated their impact in NETosis, oxidative burst and spreading applying pharmacological approach. Using specific inhibitors of PKC isoforms, we showed that PKCfi, PKC8, and PKC zeta are involved in the oxidative burst, spreading and NETosis activated by calcium ionophore A23187, while only PKCfi is implicated in these functions activated by phorbol 12-myristate 13-acetate (PMA). The data obtained in our study might help in the devel-opment of new drugs useful for the treatment of autoimmune and inflammatory diseases associated with NETs.

Automated summary

Neutrophils release extracellular traps (NETs) as a last suicidal resource in the fight against infection, but they also play a role in autoimmune, inflammatory and malignant diseases. The study investigated the role of protein kinase C (PKC) isoforms in NETosis, oxidative burst, and spreading. The findings suggest that PKCfi, PKC8, and PKC zeta are involved in NETosis activated by calcium ionophore A23187, while PKCfi is implicated in functions activated by phorbol 12-myristate 13-acetate (PMA).