Dysregulated neutrophil responses and neutrophil extracellular trap formation and degradation in PAPA syndrome

Mistry, Pragnesh; Carmona‐Rivera, Carmelo; Ombrello, Amanda K.; Hoffmann, Patrycja; Seto, Nickie; Jones, Anne; Stone, Deborah L.; Naz, Faiza; Carlucci, Philip M.; Dell’Orso, Stefania; Gutierrez-Cruz, Gustavo; Sun, Hongwei; Kastner, Daniel L.; Aksentijevich, Ivona; Kaplan, Mariana J.

doi:10.1136/annrheumdis-2018-213746

Cited by 78 publications

(85 citation statements)

References 49 publications

(107 reference statements)

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“…Humans Most of our knowledge of neutrophil heterogeneity in chronic inflammation derives from studies performed in autoimmune diseases [54,96]. In these studies, the presence of LDNs has been consistently reported in patients with systemic lupus erythematosus (SLE), psoriasis, chronic granulomatous disease, ANCA-associated systemic vasculitis, rheumatoid arthritis (RA), juvenile idiopathic arthritis, and pyogenic arthritis-pyoderma gangrenosum-acne syndrome [54,[96][97][98][99][100]. As opposed to immunosuppressive LDNs/PMN-MDSCs, LDNs from autoimmune patients have been defined as low-density granulocytes (LDGs) (Box 1 and Figure 3) based on their proinflammatory properties [4,7,54,96], including the promotion of Th17 cell differentiation and proliferation [101].…”

Section: Neutrophil Diversity and Heterogeneity In Chronic Inflammationmentioning

confidence: 99%

“…As opposed to immunosuppressive LDNs/PMN-MDSCs, LDNs from autoimmune patients have been defined as low-density granulocytes (LDGs) (Box 1 and Figure 3) based on their proinflammatory properties [4,7,54,96], including the promotion of Th17 cell differentiation and proliferation [101]. It is important to note that the distinction between LDNs/LDGs and LDNs/PMN-MDSCs is based only on functional assays performed on isolated cells because no validated markers have been identified that can discriminate between suppressive and proinflam- or 'low-density granulocytes' (LDGs) (Box 1) have been found in patients with autoimmune diseases, including systemic lupus erythematosus (SLE), psoriasis, chronic granulomatous disease, anti-neutrophil cytoplasmic autoantibody (ANCA)associated vasculitis, rheumatoid arthritis (RA), juvenile idiopathic arthritis, and pyogenic arthritis-pyoderma gangrenosumacne syndrome [96][97][98][99][100]. However, not all studies tested/reported the proinflammatory properties of LDNs from autoimmune patients.…”

Section: Neutrophil Diversity and Heterogeneity In Chronic Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

Neutrophil Diversity in Health and Disease

Silvestre-Roig

Fridlender

Glogauer

et al. 2019

Trends in Immunology

326

279

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Section: Neutrophil Diversity and Heterogeneity In Chronic Inflammationmentioning

confidence: 99%

Section: Neutrophil Diversity and Heterogeneity In Chronic Inflammationmentioning

confidence: 99%

Neutrophil Diversity in Health and Disease

Silvestre-Roig

Fridlender

Glogauer

et al. 2019

Trends in Immunology

326

279

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“…The results showed that only at the concentration of 1.6 µM, BPA modulated neutrophil functions related to absorption. These observations appear to be particularly concerning in the case of people who are professionally exposed to BPA, considering the fact that the phagocytic activity is the rst line of defense against many pathogens [9][10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

“…One of the strategies used by neutrophils to kill pathogens is phagocytosis, which involves the stages such as "recognition" and "absorption" of the pathogen and formation of a phagolysosome. Inside the phagolysosome, the absorbed pathogen is killed by any of the two mechanisms: aerobic (associated with the production of reactive oxygen species (ROS) and reactive nitrogen species) and anaerobic (associated with the presence of proteins contained in the granules) [7,[9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Sex-dependent dysregulation of human neutrophil responses by bisphenol A

Ratajczak–Wrona

Garley

Rusak

et al. 2020

Preprint

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Background: In the present study, we aimed to investigate selected functions of human neutrophils exposed to bisphenol A (BPA) under in vitro conditions. As BPA is classified among xenoestrogens, we compared its action and effects with those of 17β-estradiol (E2).Methods: Chemotaxis of neutrophils was examined using the Boyden chamber. Their phagocytosis and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity were assessed via Park’s method with latex beads and Park’s test with nitroblue tetrazolium . To assess the total concentration of nitric oxide (NO), the Griess reaction was utilized. Flow cytometry was used to assess the expression of cluster of differentiation (CD) antigens. The formation of neutrophil extracellular traps (NETs) was analyzed using a microscope (IN Cell Analyzer 2200 system). Expression of the investigated proteins was determined using Western blot.Results: The analysis of results obtained for both sexes demonstrated that after exposure to BPA, the chemotactic capacity of neutrophils was reduced. In the presence of BPA, the phagocytic activity was found to be elevated in the cells obtained from women and reduced in the cells from men. Following exposure to BPA, the percentage of neutrophils with CD14 and CD284 (TLR4) expression, as well as the percentage of cells forming NETs, was increased in the cells from both sexes. The stimulatory role of BPA and E2 in the activation of NADPH oxidase was observed only in female cells. On the other hand, no influence of E2 on the expression of CD14 and CD284, chemotaxis, phagocytosis, and the amount of NET-positive neutrophils was found for both sexes. The study further showed that BPA intensified NO production and iNOS expression in the cells of both sexes. In addition, intensified expression of all tested PI3K-Akt pathway proteins was observed in male neutrophils.Conclusions: The study demonstrated the influence of BPA on neutrophil functions associated with locomotion and pathogen elimination, which in turn may disturb the immune response of these cells in both women and men. Analysis of the obtained data showed that the effect of this xenoestrogen on the human neutrophils was more pronounced than E2.

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“…Flares of sterile arthritis with neutrophil infiltrate and the overproduction of IL-1β are the main features of pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome. NETs have been identified in the skin lesions of a patient with active PAPA syndrome in a milieu characterized by IL-1β, IL-8, and IL-17A expression, but not in skin samples from a patient with no active skin lesions 96 . In vitro, serum of PAPA patients induced NET formation by neutrophils from healthy donors that could be blocked by the IL-1 receptor antagonist anakinra, suggesting that IL-1β contributes to the enhanced NET formation in PAPA 96 .…”

Section: Nets In Autoinflammatory Diseasesmentioning

confidence: 94%

In vivo evidence for extracellular DNA trap formation

et al. 2020

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Extracellular DNA trap formation is a cellular function of neutrophils, eosinophils, and basophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form extracellular traps, granulocytes release a scaffold consisting of mitochondrial DNA in association with granule proteins. As we understand more about the molecular mechanism for the formation of extracellular DNA traps, the in vivo function of this phenomenon under pathological conditions remains an enigma. In this article, we critically review the literature to summarize the evidence for extracellular DNA trap formation under in vivo conditions. Extracellular DNA traps have not only been detected in infectious diseases but also in chronic inflammatory diseases, as well as in cancer. While on the one hand, extracellular DNA traps clearly exhibit an important function in host defense, it appears that they can also contribute to the maintenance of inflammation and metastasis, suggesting that they may represent an interesting drug target for such pathological conditions. Facts •The demonstration of extracellular DNA traps in vivo requires sections of affected tissues, which are to be investigated with special staining techniques. These structures are seen in multiple inflammatory and cancer diseases.Is there a simple biomarker that reflects extracellular DNA trap formation?• What is the contribution of extracellular microbe killing compared to intracellular killing following phagocytosis?• The mechanism of DNA trap formation is unknown.

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Dysregulated neutrophil responses and neutrophil extracellular trap formation and degradation in PAPA syndrome

Cited by 78 publications

References 49 publications

Neutrophil Diversity in Health and Disease

Neutrophil Diversity in Health and Disease

Sex-dependent dysregulation of human neutrophil responses by bisphenol A

In vivo evidence for extracellular DNA trap formation

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