scholarly journals The Dual Role of Myeloperoxidase in Immune Response

2020 ◽  
Vol 21 (21) ◽  
pp. 8057 ◽  
Author(s):  
Jürgen Arnhold
Keyword(s):  
Immune Response ◽  
Innate Immune System ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Major Constituent ◽  
Extracellular Traps ◽  
Atherosclerotic Lesions ◽  
Disease Specific ◽  
Frustrated Phagocytosis

The heme protein myeloperoxidase (MPO) is a major constituent of neutrophils. As a key mediator of the innate immune system, neutrophils are rapidly recruited to inflammatory sites, where they recognize, phagocytose, and inactivate foreign microorganisms. In the newly formed phagosomes, MPO is involved in the creation and maintenance of an alkaline milieu, which is optimal in combatting microbes. Myeloperoxidase is also a key component in neutrophil extracellular traps. These helpful properties are contrasted by the release of MPO and other neutrophil constituents from necrotic cells or as a result of frustrated phagocytosis. Although MPO is inactivated by the plasma protein ceruloplasmin, it can interact with negatively charged components of serum and the extracellular matrix. In cardiovascular diseases and many other disease scenarios, active MPO and MPO-modified targets are present in atherosclerotic lesions and other disease-specific locations. This implies an involvement of neutrophils, MPO, and other neutrophil products in pathogenesis mechanisms. This review critically reflects on the beneficial and harmful functions of MPO against the background of immune response.

scholarly journals Neutrophils and NETs in modulating acute and chronic inflammation

Blood ◽  
2019 ◽  
Vol 133 (20) ◽  
pp. 2178-2185 ◽  
Author(s):  
Fernanda V. S. Castanheira ◽  
Paul Kubes
Keyword(s):  
Chronic Inflammation ◽  
Host Defense ◽  
Innate Immune System ◽  
Tissue Repair ◽  
Essential Role ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Extracellular Traps ◽  
Acute And Chronic Inflammation

Abstract Neutrophils are an absolutely essential part of the innate immune system, playing an essential role in the control of infectious diseases but more recently are also being viewed as important players in tissue repair. Neutrophils are able to counteract an infection through phagocytosis and/or the release of neutrophil extracellular traps (NETs). By contrast, neutrophils help repair damaged tissues, limiting NET production but still phagocytosing debris. However, when inflammation is recurrent, or the inciting agent persists, neutrophils through a frustrated inability to resolve the problem can release NETs to exacerbate tissue damage during inappropriate inflammation. In this review, we discuss the mechanisms of NET formation, as well as the apparent paradoxical role of neutrophils and NETs in host defense, chronic inflammation, and tissue disrepair.

scholarly journals Role of Neutrophils on the Ocular Surface

2021 ◽  
Vol 22 (19) ◽  
pp. 10386
Author(s):  
Yongseok Mun ◽  
Jin Sun Hwang ◽  
Young Joo Shin
Keyword(s):  
Ocular Surface ◽  
Innate Immune System ◽  
Neutrophil Infiltration ◽  
Neutrophil Extracellular Traps ◽  
Therapeutic Agents ◽  
Innate Immune ◽  
Neutrophil Extracellular Trap ◽  
Extracellular Traps ◽  
Ocular Surface Diseases

The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.

scholarly journals Start a fire, kill the bug: The role of platelets in inflammation and infection

2018 ◽  
Vol 24 (6) ◽  
pp. 335-348 ◽  
Author(s):  
Carsten Deppermann ◽  
Paul Kubes
Keyword(s):  
Immune Cells ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Oxygen Species ◽  
Vascular Integrity ◽  
Surface Receptors ◽  
Extracellular Traps

Platelets are the main players in thrombosis and hemostasis; however they also play important roles during inflammation and infection. Through their surface receptors, platelets can directly interact with pathogens and immune cells. Platelets form complexes with neutrophils to modulate their capacities to produce reactive oxygen species or form neutrophil extracellular traps. Furthermore, they release microbicidal factors and cytokines that kill pathogens and influence the immune response, respectively. Platelets also maintain the vascular integrity during inflammation by a mechanism that is different from classical platelet activation. In this review we summarize the current knowledge about how platelets interact with the innate immune system during inflammation and infection and highlight recent advances in the field.

scholarly journals Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Elcha Charles ◽  
Benjamin L. Dumont ◽  
Steven Bonneau ◽  
Paul-Eduard Neagoe ◽  
Louis Villeneuve ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Extracellular Traps ◽  
Pathological Conditions ◽  
Healthy Control ◽  
Angiopoietin 1

Abstract Background Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM. Results Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF without (w/o) T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF w/o T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin. Conclusions Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.

Natural Killer Cells Induce the Formation of Neutrophil Extracellular Traps (NETs) in Venous Thrombosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1424-1424
Author(s):  
François-René Bertin ◽  
Sandrine Laurance ◽  
Catherine Lemarie ◽  
Mark Blostein
Keyword(s):  
Venous Thrombosis ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Flow Restriction ◽  
Extracellular Traps

Abstract Thrombosis is considered to be a pathological deviation of physiologic hemostasis involving similar mechanisms. Interestingly, recent work demonstrates that innate immune cells promote venous thrombosis. Innate immune cells were shown to collaborate to induce the activation of the coagulation cascade and platelets. In particular, neutrophils contribute to venous thrombosis through the release of neutrophil extracellular traps (NETs). However, the mechanism triggering the formation of NETs during venous thrombosis remain unknown. Of interest, a study showed that IFNγ induced the formation of NETs. Thus, we investigated the role of IFNγ-producing cells in the development of thrombosis. We used mice lacking IFNγ, Tbet (the transcription factor regulating the expression of IFNγ) or wild type mice. Venous thrombosis was induced using the flow restriction model in the inferior vena cava , as has been previously published. In Tbet-/-, IFNγ-/- and WT mice, we show that the absence of Tbet or IFNγ decreases the formation of thrombi after venous thrombosis induction, suggesting that the Tbet+/IFNγ producing cells are required for the early development of venous thrombosis. Comparing the composition of the thrombi from Tbet-/-, IFNγ-/- and WT mice, we show that, in all mice, neutrophils are the main cellular component of thrombi followed by monocytes; however, the number of neutrophil extracellular traps (NETs) formed during thrombosis is significantly lower in Tbet-/- and IFNγ-/- mice. Furthermore, NET formation is also decreased in WT mice specifically depleted of IFNγ and increases in Tbet-/- and IFNγ-/- mice injected with recombinant IFNγ. In vitro, we show that stimulation of WT murine neutrophils with recombinant IFNγ triggers the formation of NETs demonstrating that Tbet and IFNγ are crucial for NET formation by neutrophils. Natural killer (NK) cells are the main producers of IFNγ . Thus, we investigated the role of NK cells in venous thrombosis induced by flow restriction. NK cells were specifically depleted with an antibody during the development of venous thrombosis. The absence of NK cells results in smaller thrombi suggesting that NK cells are required for early thrombus development. Additionally, depletion in NK cells results in decreased in-situ IFNγ production and decreased NET formation. To directly link NK cells to the formation of NETs, WT neutrophils were co-cultured with Tbet-/- and IFNγ-/- NK cells. We show that WT neutrophils release less NETs when cultured with Tbet-/- and IFNγ-/- NK cells as compared to WT NK cells. These data suggest that NK cells trigger the formation of NETs by neutrophils through the production of IFNγ. Hence, we demonstrate that, in a partial flow restriction model of venous thrombosis, Tbet and IFNγ are crucial for thrombus development by promoting the formation of NETs by neutrophils and that NK cells are key effector cells in this process. Disclosures Blostein: boehringer-ingelheim: Research Funding.

scholarly journals Inflammation and Epilepsy

2005 ◽  
Vol 5 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Annamaria Vezzani
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Innate Immune System ◽  
Structural Changes ◽  
Seizure Activity ◽  
Experimental Models ◽  
Innate Immune ◽  
Inflammatory Reactions ◽  
Inflammatory Processes

In recent years, increasing evidence has indicated that immune and inflammatory reactions occur in brain in various central nervous system (CNS) diseases. Furthermore, inflammatory processes, such as the production of proinflammatory cytokines and related molecules, have been described in brain after seizures induced in experimental models and in clinical cases of epilepsy. Although little is known about the role of inflammation in epilepsy, it has been hypothesized that activation of the innate immune system and associated inflammatory reactions in brain may mediate some of the molecular and structural changes occurring during and after seizure activity. Whether the innate immune response that takes place in epileptic tissue is beneficial or noxious to the CNS is still an open and intriguing question that should be addressed by further investigations.

358 Trial in progress: A pilot study of combined immune checkpoint inhibition in combination with ablative therapies in subjects with hepatocellular carcinoma (HCC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A383-A383
Author(s):  
Hailey Carroll ◽  
Umair Aleem ◽  
Pooja Varghese ◽  
Marie Galligan ◽  
Michèle Bourke ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint ◽  
Innate Immune System ◽  
Innate Immune ◽  
University Hospital ◽  
Advanced Hepatocellular Carcinoma ◽  
Ablative Therapies

BackgroundLocoregional therapies for hepatocellular carcinoma, such as transcatheter arterial chemoembolization (TACE) or ablation, can induce a peripheral anti-tumor immune response. This may be amplified by immune checkpoint inhibitors (ICI). Early and higher anti-CTLA4 dosing could potentially lead to better priming and a stronger immune response. Recent data has suggested that early (Day 1 only), increased doses of anti-CTLA4 therapy, was associated with encouraging clinical activity and a tolerable safety profile. This study will evaluate dual immune checkpoint, CTLA4 (tremelimumab, day 1-only dosing) and PD-L1 (durvalumab) blockade in combination with TACE in patients with advanced HCC. Intensive peripheral immune-monitoring and longitudinal on-treatment tumor biopsies will focus on the role of the innate immune system, particularly Natural Killer cells, in anti-tumor responses.MethodsPatients with HCC (Childs Pugh A/B7; Barcelona Clinic Liver Cancer Stage B/C; ECOG 0/1; sorafenib-naïve or experienced) are being enrolled in a pilot study (Study Number UCDCRC/19/01) of tremelimumab at 2 dose levels (DL1 and DL2) in combination with durvalumab and TACE until disease progression (per irRECIST). DL1: tremelimumab (75 mg q28 days for 4 doses) and durvalumab (1500 mg q28 days). DL2: tremelimumab (300 mg in a single dose on day 1) and durvalumab (1500 mg q28 days). Subtotal TACE will be performed during study week 6 with the dose-limiting toxicity (DLT) evaluation period encompassing the first 8 weeks of the study. Primary endpoint is 6-month progression-free survival with secondary efficacy endpoints being safety, tolerability and overall survival. Exploratory objectives will evaluate changes in immune parameters in the tumor and peripheral blood of patients undergoing anti-CTLA4 therapy pre- and post-RFA or TACE. A major focus will be on the role of the innate immune system, particularly Natural Killer cells, in anti-tumor responses. Patients will be enrolled and treated at St Vincent’s University Hospital in Dublin, Ireland. This study is currently open and actively recruiting.ResultsN/AConclusionsN/ATrial RegistrationEudraCT Number 2019-002767-98Ethics ApprovalSt Vincent’s University Hospital Research Ethics Committee Study Number UCDCRC/19/01.ReferencesDuffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol 2017;66(3):545–51.Lencioni R, Petruzzi P, Crocetti L. Chemoembolization of hepatocellular carcinoma. Semin Intervent Radiol 2013;30(1):3–11.Slovak R, Ludwig JM, Gettinger SN, Herbst RS, Kim HS. Immuno-thermal ablations – boosting the anticancer immune response.Mehta A, Oklu R, Sheth RA. Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response?Gastroenterol Res Pract2016; 2016:9251375.Ng J, Dai T. Radiation therapy and the abscopal effect: a concept comes of age. Ann Transl Med 2016;4(6):118.O’Brien MA, Power DG, Clover AJ, Bird B, Soden DM, Forde PF. Local tumour ablative therapies: opportunities for maximising immune engagement and activation. Biochim Biophys Acta2014; 1846(2):510–23.Kelley RK, Sangro B, Harris WP, Ikeda M, Okusaka T, Kang Y-K, et al. Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC). Journal of Clinical Oncology 2020;38(15_suppl):4508-.Mariniello A, Novello S, Scagliotti GV, Ramalingam SS. Double immune checkpoint blockade in advanced NSCLC. Crit Rev Oncol Hematol 2020;152:102980.

scholarly journals Angiopoietin 1 release from Human Neutrophils is Independent from Neutrophil Extracellular Traps (NETs)

2021 ◽  
Author(s):  
Elcha Charles ◽  
Benjamin Dumont ◽  
Steven Bonneau ◽  
Paul-Eduard Neagoe ◽  
Louis Villeneuve ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Extracellular Traps ◽  
Pathological Conditions ◽  
Healthy Control ◽  
Angiopoietin 1

Abstract Background: Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM. Results: Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF w/o T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF without T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin. Conclusions: Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.

Sign in / Sign up

Export Citation Format

Share Document