Saffarzadeh Mona, Cabrera-Fuentes Hector A, Veit Florian, Jiang Dongsheng, Scharffetter-Kochanek Karin, Gille Christian Gille, Rooijakkers Suzan H M, Hartl Dominik, Preissner Klaus T
Department of Biochemistry, School of Medicine, Justus-Liebig-University, Giessen, Germany.
Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Mainz, Germany.
Discoveries (Craiova). 2014 Jun 30;2(2):e19. doi: 10.15190/d.2014.11.
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.
中性粒细胞作为先天性宿主防御的第一道细胞防线，通过吞噬作用和形成中性粒细胞胞外陷阱（NETs）来对抗感染。佛波酯诱导的经典NET形成需要数小时才能完成。然而，最近的研究表明，血小板、金黄色葡萄球菌或真菌产物刺激中性粒细胞后会迅速形成NETs。在此我们描述了抗体或补体诱导的吞噬作用会触发快速NET形成。与经典的NETosis不同，NADPH氧化酶的化学抑制以及使用NADPH氧化酶缺陷患者的中性粒细胞并不影响快速NET形成。虽然吞噬作用和快速NET形成可能不是彼此的先决条件，但吞噬作用与快速NET形成的协同作用可能对提高对抗播散性细菌的防御机制效率至关重要。剖析NET形成的不同机制对于开发针对NETs起关键作用的感染性和自身免疫性疾病的新型治疗策略至关重要。
