Potent NETosis inducers do not show synergistic effects in vitro
| Autor: | Urszula Demkow, Michal Przemyslaw Pruchniak |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
autoimmunity
lcsh:R Immunology neutrophil extracellular traps lcsh:Medicine chemistry.chemical_element Stimulation Neutrophil extracellular traps Calcium neutrophil cross-stimulation netosis In vitro Complement system Proinflammatory cytokine Cell biology Extracellular matrix 03 medical and health sciences 0302 clinical medicine Immune system chemistry Immunology and Allergy Clinical Immunology 030215 immunology |
| Zdroj: | Central European Journal of Immunology, Vol 44, Iss 1, Pp 51-58 (2019) Central-European Journal of Immunology |
| ISSN: | 1426-3912 |
| DOI: | 10.5114/ceji.2019.84017 |
| Popis: | Introduction NETosis is a process whereby neutrophils release chromatin into the surrounding extracellular matrix to form neutrophil extracellular traps (NETs). Under physiological conditions NETosis can be initiated by a variety of stimuli, including immune complexes, complement activation products, and a milieu of proinflammatory cytokines. Because overproduction of NETs is often related to the promotion or aggravation of autoimmune responses, we decided to assess how simultaneous activation of NETosis by different stimuli affects NET production. Material and methods NET formation was initiated by using combinations of three different NETosis inducers: phorbol myristate acetate (PMA), N-formylmethionyl-leucyl-phenylalanine (fMLP) and calcium ionophore (CaI). We measured fluorometry in real time, while microscopic visualisation served as an additional control for NET release. In total, 30 subjects free from infections or chronic diseases were enrolled in this study. Results We were able to demonstrate that in all cases NETosis induced by a combination of two stimuli resulted in diminished NETs production when compared to PMA and CaI single stimulations (p ≤ 0.001). The only cases in which double stimulation showed similar results to single stimulation were when we compared fMLP + CaI stimulation with fMLP single stimulation. Furthermore, when neutrophils were exposed to all three stimuli NETosis was almost entirely inhibited, compared to any single stimulation (p ≤ 0.001). Conclusions Our results show that simultaneous stimulation of neutrophils by different NETosis-inducing agents results in diminished formation of NETs compared to a single stimulation. This indicates that cells may possess an internal regulatory mechanism that prevents overgeneration of NETs among healthy people. |
| Databáze: | OpenAIRE |
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