Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1

Peng, Hsin‐Hsin; Liu, Yu-Ju; Ojcius, David M.; Lee, Chiou-Mei; Chen, Ren-Hao; Huang, Peng; Martel, Jan; Young, John Ding‐E

doi:10.1038/s41598-017-16778-4

Cited by 48 publications

(42 citation statements)

References 76 publications

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“…Interestingly, tissue‐infiltrating neutrophils were found to engulf seemingly indigestible crystals in JDM. The interactions of neutrophils with a wide range of crystals, including cocaine crystals, uric acid crystals, mineralo‐organic particles, and cholesterol crystals, have been previously described . In accordance with findings from prior investigations, we were able to demonstrate that calcium crystals, either BCP or patient‐derived crystals, had the capacity to engage neutrophils to induce a process referred to as “frustrated phagocytosis” and subsequent NET formation.…”

Section: Discussionsupporting

confidence: 90%

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Neutrophil Extracellular Traps in Tissue and Periphery in Juvenile Dermatomyositis

Duvvuri

Pachman

Morgan

et al. 2020

Arthritis & Rheumatology

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Objective. Neutrophils are key immune cells participating in host defense through several mechanisms, including the formation of neutrophil extracellular traps (NETs). This study was undertaken to investigate the role of neutrophils in juvenile dermatomyositis (JDM).Methods. Electron microscopy was used to identify neutrophils in tissue. NETs were also imaged using fluorescence microscopy and quantified using a myeloperoxidase-DNA enzyme-linked immunosorbent assay (ELISA) in plasma obtained from healthy children (n = 20), disease controls (n = 29), JDM patients (n = 66), and JDM patients with history of calcifications (n = 20). Clinical data included disease activity scores and complement C4 levels. Levels of immune complexes (ICs) and calprotectin were analyzed using ELISA.Results. Using electron microscopy, neutrophils were found to infiltrate affected muscle tissue, engulfing deposited calcium crystals. Uptake of the crystals led to neutrophil activation (P < 0.01) and subsequent phosphatidylinositol 3-kinase-and NADPH oxidase-dependent but peptidylarginine deiminase 4-independent formation of NETs, which contained mitochondrial DNA (P < 0.05), as confirmed in vivo (P < 0.001) and in vitro (P < 0.01). Peripheral NET levels were associated with calcinosis (P = 0.01), ICs (P = 0.008), and interleukin-8 levels (P = 0.004). Children with JDM had impaired NET clearance (P = 0.01), associated with autoantibody profiles including melanoma differentiationassociated protein 5 (P = 0.005), and depressed complement C4 levels (r = −0.72, P = 0.002). Furthermore, children with JDM showed evidence of neutrophil activation, with elevated levels of peroxidase activity (P = 0.02) and calprotectin (P < 0.01), which were associated with disease activity (P = 0.007), and dyslipidemia (odds ratio 4.7, P < 0.05).Conclusion. We found novel mechanisms of both calcium crystal-mediated neutrophil activation and cell death in JDM pathophysiology. Targeting this pathway may reduce the frequency and extent of calcinosis, as well as prevent long-term development of comorbidities, including atherosclerosis.

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Section: Discussionsupporting

confidence: 90%

“…Briefly, as elegantly demonstrated by Branzk and colleagues, once the target is beyond the size of being engulfed, the neutrophil will become frustrated and undergo NETosis . Similar mechanisms also seem to apply to crystalline size . Though most crystals induce NET formation, the underlying signaling requirements are somewhat distinct.…”

Section: Discussionmentioning

confidence: 94%

Neutrophil Extracellular Traps in Tissue and Periphery in Juvenile Dermatomyositis

Duvvuri

Pachman

Morgan

et al. 2020

Arthritis & Rheumatology

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“…NAC directly functions as an oxygen radical scavenger and it is also a precursor of glutathione, which is an innate cellular antioxidant and maintains redox balance [14]. APDC acts as a glutamate receptor agonist and inhibits NADPH oxidase-dependent ROS production [50]. Generally, quinones have been observed to produce ROS by activating NADPH oxidases [51].…”

Section: Discussionmentioning

confidence: 99%

Resvega Alleviates Hydroquinone-Induced Oxidative Stress in ARPE-19 Cells

Bhattarai

Korhonen

Toppila

et al. 2020

IJMS

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Retinal pigment epithelial (RPE) cells maintain homeostasis at the retina and they are under continuous oxidative stress. Cigarette smoke is a prominent environmental risk factor for age-related macular degeneration (AMD), which further increases the oxidant load in retinal tissues. In this study, we measured oxidative stress and inflammatory markers upon cigarette smoke-derived hydroquinone exposure on human ARPE-19 cells. In addition, we studied the effects of commercial Resvega product on hydroquinone-induced oxidative stress. Previously, it was observed that Resvega induces autophagy during impaired protein clearance in ARPE-19 cells, for which it has the potential to alleviate pro-inflammatory pathways. Cell viability was determined while using the lactate dehydrogenase (LDH) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and the cytokine levels were measured using the enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) production were measured using the 2′,7′-dichlorofluorescin diacetate (H2DCFDA) probe. Hydroquinone compromised the cell viability and increased ROS production in ARPE-19 cells. Resvega significantly improved cell viability upon hydroquinone exposure and reduced the release of interleukin (IL)-8 and monocytic chemoattractant protein (MCP)-1 from RPE cells. Resvega, N-acetyl-cysteine (NAC) and aminopyrrolidine-2,4-dicarboxylic acid (APDC) alleviated hydroquinone-induced ROS production in RPE cells. Collectively, our results indicate that hydroquinone induces cytotoxicity and increases oxidative stress through NADPH oxidase activity in RPE cells, and resveratrol-containing Resvega products prevent those adverse effects.

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“…HMGB1 has also been reported to be present on NETs and thereby to stimulate macrophages. 67 In a simple experiment in which whole blood was perfused over pre-formed NETs, platelets were shown to be recruited to NETs specifically. 68 Platelets might bind to C3b deposits on NETs because platelets express CR1 on their membrane.…”

Section: The Interplay Of Coagulation and Netosismentioning

confidence: 99%

NETosis, complement, and coagulation: a triangular relationship

2018

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NETosis is a regulated form of neutrophil cell death that contributes to the host defense against pathogens and was linked to various diseases soon after its first description in 2004. During NETosis, neutrophils release neutrophil extracellular traps (NETs), which can capture and kill bacteria and other pathogens to prevent them from spreading. Although substantial progress has been made in our understanding of NETosis, the precise mechanism underlying NETosis is still a matter of debate. Research continues to elucidate the molecular pathways involved in NETosis. In recent years, interactions with the complement and coagulation systems have become increasingly apparent. Activated complement proteins can stimulate NET formation, and NETs, in turn, can serve as a platform for complement activation. In addition, NETs can act as a scaffold for thrombus formation during coagulation. While crosstalk between the coagulation and complement systems has been previously described, NETosis appears to be a third important player in this consortium to protect the host against pathogens. This review summarizes our current knowledge on the mutual interactions between NETosis, the complement system and the coagulation system, with an emerging description of their complex triangular relationship.

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Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1

Cited by 48 publications

References 76 publications

Neutrophil Extracellular Traps in Tissue and Periphery in Juvenile Dermatomyositis

Neutrophil Extracellular Traps in Tissue and Periphery in Juvenile Dermatomyositis

Resvega Alleviates Hydroquinone-Induced Oxidative Stress in ARPE-19 Cells

NETosis, complement, and coagulation: a triangular relationship

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