Characterization of rapid neutrophil extracellular trap formation and its cooperation with phagocytosis in human neutrophils

Mona Saffarzadeh; Hector A Cabrera-Fuentes; Florian Veit; Dongsheng Jiang; Karin Scharffetter-Kochanek; Christian Gille Gille; Suzan H M Rooijakkers; Dominik Hartl; Klaus T Preissner

doi:10.15190/d.2014.11

Characterization of rapid neutrophil extracellular trap formation and its cooperation with phagocytosis in human neutrophils

Discoveries (Craiova). 2014 Jun 30;2(2):e19. doi: 10.15190/d.2014.11.

Authors

Mona Saffarzadeh^{1

2}, Hector A Cabrera-Fuentes¹, Florian Veit³, Dongsheng Jiang⁴, Karin Scharffetter-Kochanek⁴, Christian Gille Gille⁵, Suzan H M Rooijakkers⁶, Dominik Hartl⁷, Klaus T Preissner¹

Affiliations

¹ Department of Biochemistry, School of Medicine, Justus-Liebig-University, Giessen, Germany.
² Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Mainz, Germany.
³ Excellence Cluster Cardio-Pulmonary System (ECCPS), German Lung Center (DZL), Justus-Liebig-University Giessen, Giessen, Germany.
⁴ Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
⁵ Department of Pediatrics IV/Neonatology, Eberhard Karls University, Tuebingen, Germany.
⁶ Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁷ Department of Pediatrics I, Eberhard Karls University, Tuebingen, Germany.

Abstract

Neutrophils, as the first cellular line of innate host defense, employ phagocytosis and formation of neutrophil extracellular traps (NETs) to combat infections. Classical NET formation induced by phorbol myristate acetate requires several hours to complete. However, recent studies demonstrated rapid NET formation in neutrophils upon stimulation by platelets, Staphylococcus aureus or fungal products. Here we describe that antibody- or complement-induced phagocytosis triggers rapid NET formation. In contrast to classical NETosis, chemical inhibition of NADPH oxidase as well as using NADPH oxidase-deficient patient neutrophils did not affect rapid NET formation. Although phagocytosis and rapid NET formation may not be the prerequisite of each other, cooperation of phagocytosis and rapid NET formation may be essential to improve the efficiency of defense mechanisms in combating disseminating bacteria. Dissecting the differential mechanisms of NET formation is crucial to develop novel therapeutic strategies for infectious and auto-immune diseases where NETs play an essential role.

Keywords: Neutrophil extracellular traps (NETs); Phagocytosis; Rapid NETosis.