Review
Biochemistry & Molecular Biology
Jose M. Rodrigo-Munoz, Marta Gil-Martinez, Beatriz Sastre, Victoria del Pozo
Summary: Eosinophils are complex immune cells with diverse functions in various organs and can be both beneficial and detrimental to human health. While our understanding of eosinophils continues to evolve, their roles in homeostasis and disease remain complex and multifaceted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Microbiology
Juliana da Costa Silva, Glaucia de Azevedo Thompson-Souza, Marina Valente Barroso, Josiane Sabbadini Neves, Rodrigo Tinoco Figueiredo
Summary: Fungal infections are a global health problem, with neutrophils and eosinophils playing key roles in controlling fungal infections by releasing extracellular traps (ETs) that exhibit antifungal activities.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell Biology
Nina Germic, Timothee Fettrelet, Darko Stojkov, Aref Hosseini, Michael P. Horn, Alexander Karaulov, Dagmar Simon, Shida Yousefi, Hans-Uwe Simon
Summary: This study investigated the time-dependent release of EPX and mtDNA in activated human and mouse eosinophils. The results showed rapid degranulation within 1 minute and slower release of mtDNA reaching maximal levels between 30 and 60 minutes. These data suggest different molecular pathways for degranulation and mtDNA release, with the association between mtDNA scaffold and granule proteins likely occurring in the extracellular space.
Review
Immunology
Darko Stojkov, Lea Gigon, Shuang Peng, Robert Lukowski, Peter Ruth, Alexander Karaulov, Albert Rizvanov, Nickolai A. Barlev, Shida Yousefi, Hans-Uwe Simon
Summary: Neutrophils, the most abundant cells in the leukocyte population, can modulate glycolysis and other metabolic pathways to limit their effector functions. These metabolic pathways are crucial for energy usage and specialized actions, such as ROS production, chemotaxis, phagocytosis, degranulation, and the formation of NETs. Understanding the requirements of metabolic pathways for neutrophil functions may lead to the discovery of molecular targets for novel anti-infectious and/or anti-inflammatory drugs.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Allergy
Siyuan Zhang, Zhenlin Wang
Summary: This article provides a comprehensive overview of recent research on neutrophil extracellular traps (NETs) and eosinophil extracellular traps (EETs) in chronic rhinosinusitis (CRS), and deepens the understanding of the functions of these extracellular traps in CRS.
CURRENT ALLERGY AND ASTHMA REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Maria Amparo Blanch-Ruiz, Raquel Ortega-Luna, Maria Angeles Martinez-Cuesta, Angeles Alvarez
Summary: Cardiovascular diseases are a leading cause of death, with blood-cell interactions and endothelial dysfunction playing a key role in thrombus formation. Neutrophil extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) have been reported to contribute to thrombosis through various mechanisms, requiring exhaustive analysis of their structure and composition to clarify their role in pathological thrombus formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Respiratory System
Kunlu Shen, Mengyuan Zhang, Ruiheng Zhao, Yun Li, Chunxiao Li, Xin Hou, Bingqing Sun, Bowen Liu, Min Xiang, Jiangtao Lin
Summary: This article examines the role of EETs in asthma, highlighting their protective effect in limiting pathogen migration and antimicrobial activity, but emphasizing that their overproduction may exacerbate allergic asthma.
RESPIRATORY RESEARCH
(2023)
Review
Hematology
Thiemo Greistorfer, Philipp Jud
Summary: Since the COVID-19 pandemic began, there have been numerous reports on the potential effects of SARS-CoV-2 infection on the cardiovascular system, leading to COVID-19-associated vascular diseases during the acute phase and measurable vascular changes during the convalescent phase. Infection with SARS-CoV-2 appears to have direct and indirect effects on the endothelium, immune system, and coagulation system, resulting in endothelial dysfunction, immunothrombosis, and the formation of neutrophil extracellular traps. This review provides an update on the pathophysiological pathways of these three major mechanisms contributing to COVID-19 vascular diseases and vascular changes, as well as their clinical implications and the significance of outcome data.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Hui Fang, Shuai Shao, Ke Xue, Xu Yuan, Pei Qiao, Jieyu Zhang, Tianyu Cao, Yixin Luo, Xiaocui Bai, Wenjing Li, Caixia Li, Hongjiang Qiao, Erle Dang, Gang Wang
Summary: Bullous pemphigoid (BP) patients exhibit abnormal neutrophil extracellular traps (NETs) in circulation, which are closely correlated with disease severity. The study demonstrates that neutrophils from BP patients display enhanced spontaneous NETs formation. Moreover, elevated levels of NETs in patients boost autoantibody production.
Article
Immunology
Vitor H. Neves, Cinthia Palazzi, Kennedy Bonjour, Shigeharu Ueki, Peter F. Weller, Rossana C. N. Melo
Summary: This study examined the ultrastructure of eosinophilic diseases using transmission electron microscopy. The findings revealed that a significant proportion of tissue-infiltrated eosinophils in various diseases undergo cytolysis and release extracellular granules. Eosinophils in early ETosis showed increased nuclear area, and ETosis led to the release of inflammatory markers.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Sicilia Rezende Oliveira, Jose Alcides Almeida de Arruda, Ayda Henriques Schneider, Valessa Florindo Carvalho, Caio Cavalcante Machado, Joice Dias Correa, Marcela Faria Moura, Leticia Fernanda Duffles, Flavio Falcao Lima de Souza, Gilda Aparecida Ferreira, Fernando Oliveira Costa, Lucas Guimaraes Abreu, Mario Taba Junior, Sandra Yasuyo Fukada, Rene Donizeti Ribeiro de Oliveira, Paulo Louzada-Junior, Fernando de Queiroz Cunha, Tarcilia Aparecida Silva
Summary: This study reveals a potential link between periodontitis and RA through the involvement of NETs, and periodontal therapy can dramatically affect circulating NET levels.
Article
Dermatology
Takahiko Sato, Takahito Chiba, Takeshi Nakahara, Ken Watanabe, Sawako Sakai, Natsuko Noguchi, Mai Noto, Shigeharu Ueki, Michihiro Kono
Summary: This study confirms the occurrence of eosinophil extracellular trap cell death and the pathological role of galectin-10 in bullous pemphigoid. Galectin-10 may contribute to blister formation in bullous pemphigoid by promoting the production of matrix metalloproteinases by keratinocytes and fibroblasts.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2023)
Article
Immunology
Charalampos Papagoras, Vasiliki Lampropoulou, Eleni Mavraki, Akrivi Chrysanthopoulou, Savas Deftereos, Juan Arostegui, Panagiotis Skendros, Konstantinos Ritis
Summary: The case study described a patient with both CAPS and MS. Inhibition of IL-1 with anakinra alleviated CAPS symptoms and, combined with teriflunomide, improved MS. In vitro studies showed that the patient's neutrophils released NETs with decorated IL-1 beta during CAPS flare, but decreased significantly after anakinra treatment, suggesting a need for further research on the role of neutrophils/NETs and IL-1 beta in MS.
CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Sverre Grover Aukrust, Kristine Bech Holte, Trine B. Opstad, Ingebjorg Seljeflot, Tore Julsrud Berg, Ragnhild Helseth
Summary: In patients with long-term T1DM, the levels of circulating NETs are not consistently associated with the presence of T1DM or the development of CAD. This suggests altered neutrophil function and reduced NETosis in T1DM.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Laura Perez-Olivares, Oliver Soehnlein
Summary: This review focuses on the active role of neutrophils and NETs as underestimated players in the inflammatory process during atherogenesis and lesion progression, how these extracellular structures communicate with main cell types in atherosclerotic lesions, and how neutrophil effector functions interact with lifestyle-derived risk factors in the development of cardiovascular disease.
Review
Oncology
Leonardo Cristinziano, Luca Modestino, Alessandro Antonelli, Gianni Marone, Hans-Uwe Simon, Gilda Varricchi, Maria Rosaria Galdiero
Summary: Neutrophils, in addition to their well-known functions in the acute phases of the immune response, play important roles in tumor initiation and progression through the release of various mediators. Neutrophil extracellular traps (NETs), composed of DNA and decorating proteins, not only trap and kill extracellular pathogens, but also have both pro-inflammatory and anti-inflammatory effects in cancer-related inflammation. This review focuses on the mechanisms underlying the emerging effects of NETs in cancer initiation and progression.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Kim Klapan, Dagmar Simon, Alexander Karaulov, Marina Gomzikova, Albert Rizvanov, Shida Yousefi, Hans-Uwe Simon
Summary: This review provides an overview of the principles of autophagy and highlights recent research on the role of autophagy in skin disorders and therapeutic modulation strategies.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shuang Peng, Darko Stojkov, Jian Gao, Kevin Oberson, Philipp Latzin, Carmen Casaulta, Shida Yousefi, Hans-Uwe Simon
Summary: This study reveals a previously unknown role of RHOH in regulating actomyosin-mediated neutrophil effector functions. RHOH, constitutively GTP-bound, limits neutrophil degranulation and the formation of neutrophil extracellular traps. RHOH achieves this by inhibiting the transport of mitochondria and granules along actin filaments, and by modulating actin polymerization through RAC1 activity. In vivo studies using Rhoh(-/-) mice demonstrate an increased antibacterial defense capability against Escherichia coli.
Review
Immunology
Shuang Peng, Jian Gao, Darko Stojkov, Shida Yousefi, Hans-Uwe Simon
Summary: Neutrophils, the most abundant innate immune cells in human blood, have been overlooked in terms of their mitochondria function. However, growing evidence shows that mitochondria play a crucial role in various aspects of neutrophil biology, from development to chemotaxis, effector function, and cell death. Mitochondria and their components can also be released by neutrophils to eliminate infection and shape immune response. This review highlights the importance of mitochondria in modulating neutrophil phenotype and function during infection and inflammation, and discusses the potential and challenges of exploiting mitochondria in neutrophils for disease treatment.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Aref Hosseini, Darko Stojkov, Timothee Fettrelet, Rostyslav Bilyy, Shida Yousefi, Hans-Uwe Simon
Summary: Neutrophil extracellular traps (NETs) and oxidative stress play important roles in the immune defense against pathogens. However, impaired clearance of NETs in the lungs of COVID-19 patients may contribute to severe respiratory syndrome infection. Through RNA sequencing (RNA-seq) and immunofluorescence and immunohistochemistry methods, the study identified increased oxidative stress and viral-related signaling pathways in COVID-19 patients' lungs. Excess neutrophil infiltration and NET formation, with oxidized extracellular DNA co-localizing with myeloperoxidase (MPO), were observed. The lipid peroxidation marker 4-hydroxynonenal (4-HNE) showed high colocalization with NETs and correlated with lung neutrophil infiltration, suggesting its potential as a marker for identifying NETs and disease severity. Local inhalation therapy to reduce lipid oxidation and NETs may benefit severely infected patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Darko Stojkov, Meike J. Claus, Evelyne Kozlowski, Kevin Oberson, Olivier P. Scharen, Charaf Benarafa, Shida Yousefi, Hans-Uwe Simon
Summary: Neutrophil extracellular traps (NETs) are released by neutrophils as DNA scaffolds coated with granule proteins to ensnare and kill bacteria. The formation of NETs can occur through independent molecular pathways in response to various stimuli. It has been thought that NET release is associated with lytic cell death, but live neutrophils can release antimicrobial NETs rapidly. Gasdermin D (GSDMD), which causes pyroptotic death in macrophages, is believed to be essential for NET formation in neutrophils. However, the study found that GSDMD is not required for NET formation and that viable neutrophils can form NETs after inflammasome activation through both canonical and noncanonical signaling pathways.
Review
Allergy
Lea Gigon, Timothee Fettrelet, Shida Yousefi, Dagmar Simon, Hans-Uwe Simon
Summary: Eosinophils are bone marrow-derived granulocytes that increase in number during type 2 inflammatory diseases. They migrate to various tissues and organs and have multiple functions through the synthesis and release of granule proteins and pro-inflammatory mediators. The functional role of eosinophils is still debated but they may play a role in host defense and tissue homeostasis.
Review
Oncology
K. F. Idrisova, H. -U. Simon, M. O. Gomzikova
Summary: It has been discovered that traditional tumor-derived cell lines do not accurately replicate the drug response and behavior of real human cancers. Consequently, more reliable tumor models that mimic the heterogeneity and patho-physiology of patient tumors are being developed. This review aims to outline the current patient-derived models of cancer, discuss their pros and cons, and highlight the progress being made in clinical trials and research in this field.
Meeting Abstract
Dermatology
Dagmar Simon, Kim Klapan, Danielle Dutoit, Christina Burgler, Shida Yousefi, Hans-Uwe Simon
ACTA DERMATO-VENEREOLOGICA
(2022)
Meeting Abstract
Medicine, General & Internal
Thomas Greuter, Alex Straumann, Yuniel Fernandez-Marrero, Nina Germic, Aref Hosseini, Shida Yousefi, Dagmar Simon, Margaret H. Collins, Christian Bussmann, Mirna Chehade, Evan S. Dellon, Glenn T. Furuta, Nirmala Gonsalves, Ikuo Hirano, Fouad J. Moawad, Luc Biedermann, Ekaterina Safroneeva, Alain M. Schoepfer, Hans-Uwe Simon
SWISS MEDICAL WEEKLY
(2022)
