Sosa-Luis Sorely Adelina, Ríos-Ríos William de Jesús, Gómez-Bustamante Ángeles Esmeralda, Romero-Tlalolini María de Los Ángeles, Aguilar-Ruiz Sergio Roberto, Baltierez-Hoyos Rafael, Torres-Aguilar Honorio
Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
Clinical Immunology Research Department of Biochemical Sciences Faculty, Universidad Autónoma "Benito Juárez" de Oaxaca, Oaxaca City, Mexico.
Immunol Res. 2021 Jun;69(3):264-274. doi: 10.1007/s12026-021-09199-z. Epub 2021 May 8.
Neutrophil extracellular traps (NETs) are networks of decondensed chromatin loaded with antimicrobial peptides and enzymes produced against microorganisms or biochemical stimuli. Since their discovery, numerous studies made separately have revealed multiple triggers that induce similar NET morphologies allowing to classify them as lytic or non-lytic. However, the variability in NET composition depending on the inducer agent and the local milieu under similar conditions has been scarcely studied. In this work, a comparative study was conducted to evaluate structural and enzymatic divergences in NET composition induced by biochemical (phorbol myristate acetate [PMA] and hypochlorous acid [HOCl]) and microbiologic (Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) stimuli, along with the presence of plasma from healthy donors or patients with systemic lupus erythematosus (SLE). The results showed a differential composition of DNA and the antimicrobial peptide cathelicidin (LL37) and a variable enzymatic activity (neutrophil elastase, cathepsin G, myeloperoxidase) induced by the different stimuli despite showing morphologically similar NETs. Additionally, SLE plasma´s presence increased DNA and LL37 release during NET induction independently of the trigger stimulus but with no enzymatic activity differences. This work provides new evidence about NET composition variability depending on the inducer stimulus and the local milieu.
中性粒细胞胞外诱捕网（NETs）是由解聚染色质构成的网络，其上负载有针对微生物或生化刺激产生的抗菌肽和酶。自其被发现以来，众多独立开展的研究揭示了多种可诱导相似NET形态的触发因素，从而能够将它们分类为溶解性或非溶解性。然而，在相似条件下，NET组成随诱导剂和局部环境的变化情况却鲜有研究。在这项研究中，我们进行了一项比较研究，以评估由生化刺激（佛波酯 [PMA] 和次氯酸 [HOCl]）和微生物刺激（白色念珠菌、金黄色葡萄球菌和铜绿假单胞菌）诱导产生的NET组成中的结构和酶学差异，同时研究健康供体或系统性红斑狼疮（SLE）患者血浆的存在情况。结果显示，尽管形态上相似，但不同刺激诱导产生的DNA和抗菌肽cathelicidin（LL37）组成存在差异，酶活性（中性粒细胞弹性蛋白酶、组织蛋白酶G、髓过氧化物酶）也各不相同。此外，SLE血浆的存在会在NET诱导过程中增加DNA和LL37的释放，且与触发刺激无关，但酶活性无差异。这项研究为NET组成随诱导刺激和局部环境的变化提供了新的证据。
