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Structural differences of neutrophil extracellular traps induced by biochemical and microbiologic stimuli under healthy and autoimmune milieus

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Abstract

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.

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Acknowledgements

The authors would like to thank MSc. Paola Ester López Díaz for the valuable discussions and technical assistance and to the Flow Cytometry Department of the Medicine and Surgery Faculty of UABJO.

Funding

This work was supported by a basic science grant (#285480) from CONACyT and by the Department of Clinical Immunology Research of the Biochemical Sciences Faculty, Universidad Autónoma “Benito Juárez” de Oaxaca. S.A.S.L. and W.R.R have doctoral fellowships of CONACyT numbers #660793 and #827788, respectively.

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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by María de los Ángeles Romero-Tlalolini, Sergio Roberto Aguilar-Ruiz, and Rafael Baltiérrez-Hoyos. Experimental analysis was performed by Sorely Adelina Sosa-Luis, William de Jesús Ríos-Ríos, and Ángeles Esmeralda Gómez-Bustamante. Honorio Torres-Aguilar wrote the first draft of the manuscript and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Honorio Torres-Aguilar.

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The project was approved by the research and ethical committees of the Hospital Regional de Alta Especialidad de Oaxaca, Mexico (approval number: HRAEO/CIC/CEI 013/16).

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Blood samples were obtained after informed consent.

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The authors declare no competing interests.

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Sosa-Luis, S.A., Ríos-Ríos, W.d., Gómez-Bustamante, Á.E. et al. Structural differences of neutrophil extracellular traps induced by biochemical and microbiologic stimuli under healthy and autoimmune milieus. Immunol Res 69, 264–274 (2021). https://doi.org/10.1007/s12026-021-09199-z

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  • DOI: https://doi.org/10.1007/s12026-021-09199-z

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