Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation

A Hakkim, TA Fuchs, NE Martinez, S Hess… - Nature chemical …, 2011 - nature.com
A Hakkim, TA Fuchs, NE Martinez, S Hess, H Prinz, A Zychlinsky, H Waldmann
Nature chemical biology, 2011nature.com
The signaling mechanisms leading to the formation of neutrophil extracellular traps (NETs),
relevant in infections, sepsis and autoimmune diseases, are poorly understood. Neutrophils
are not amenable to studies with conventional genetic techniques. Using a new chemical
genetic analysis we show that the Raf-MEK-ERK pathway is involved in NET formation
through activation of NADPH oxidase and upregulation of antiapoptotic proteins. We identify
potential targets for drugs addressing NET-associated diseases.
Abstract
The signaling mechanisms leading to the formation of neutrophil extracellular traps (NETs), relevant in infections, sepsis and autoimmune diseases, are poorly understood. Neutrophils are not amenable to studies with conventional genetic techniques. Using a new chemical genetic analysis we show that the Raf-MEK-ERK pathway is involved in NET formation through activation of NADPH oxidase and upregulation of antiapoptotic proteins. We identify potential targets for drugs addressing NET-associated diseases.
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