DAPK2 positively regulates motility of neutrophils and eosinophils in response to intermediary chemoattractants

Geering, Barbara; Stoeckle, Christina; Rozman, Sasa; Oberson, Kevin; Benarafa, Charaf; Simon, Hans-Uwe (2014). DAPK2 positively regulates motility of neutrophils and eosinophils in response to intermediary chemoattractants. Journal of leukocyte biology, 95(2), pp. 293-303. Society for Leukocyte Biology 10.1189/jlb.0813462

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The tight regulation of granulocyte chemotaxis is crucial for initiation and resolution of inflammation. Here, we show that DAPK2, a Ca(2+)/CaM-sensitive serine/threonine kinase known to modulate cell death in various cell types, is a novel regulator of migration in granulocytes. We demonstrate that human neutrophils and eosinophils express DAPK2 but unlike other leukocytes, no DAPK1 or DAPK3 protein. When DAPK activities were blocked by inhibitors, we found that neither granulocyte lifespan nor phagocytosis was affected. However, such pharmacological inactivation of DAPK activity abolished motility of granulocytes in response to intermediary but not end-target chemoattractants ex vivo. The defect in chemotaxis in DAPK2-inactive granulocytes is likely a result of reduced polarization of the cells, mediated by a lack of MLC phosphorylation, resulting in radial F-actin and pseudopod formation. As neutrophils treated with DAPKi also showed reduced recruitment to the site of inflammation in a mouse peritonitis model, DAPK2 may be a novel target for anti-inflammatory therapies.

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