Host DNases prevent vascular occlusion by neutrophil extracellular traps

Jiménez-Alcázar, Miguel; Rangaswamy, Chandini; Panda, Rachita; Bitterling, Josephine; Simsek, Yashin J.; Long, Andy; Bilyy, Rostyslav; Krenn, Veit; Renné, Christoph; Renné, Thomas; Kluge, Stefan; Panzer, Ulf; Mizuta, Ryushin; Mannherz, Hans Georg; Kitamura, Daisuke; Herrmann, Martin; Napirei, Markus; Fuchs, Tobias A.

doi:10.1126/science.aam8897

Cited by 473 publications

(498 citation statements)

References 29 publications

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“…A noncanonical pathway to vascular occlusion has recently been demonstrated [54]. It is assumed that NETs have a rather short lifetime in circulation due to the presence of serum DNases.…”

Section: A Link Between Nets Thrombosis and Innate Immunitymentioning

confidence: 99%

Neutrophil Extracellular Traps in the Second Decade

2018

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Nearly 15 years after the first description of neutrophil extracellular traps (NETs), our knowledge concerning this structure has expanded considerably. Initially, NETs were considered solely an elaborate function of the innate immune system to combat invading microorganisms. Successively it became clear that NETs have farther-reaching capabilities. They are involved in a series of pathophysiological mechanisms ranging from inflammation to thrombosis where they fulfill essential functions when produced at the right site and the right time but can have a serious impact when generation or clearance of NETs is inadequately controlled. This review provides a concise overview on the far-reaching functions of NETs in health and disease.

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“…A noncanonical pathway to vascular occlusion has recently been demonstrated [54]. It is assumed that NETs have a rather short lifetime in circulation due to the presence of serum DNases.…”

Section: A Link Between Nets Thrombosis and Innate Immunitymentioning

confidence: 99%

Neutrophil Extracellular Traps in the Second Decade

2018

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“…Interestingly, gouty tophi are composed, in part, of aggregated NETs which degrade cytokines and help in the resolution of inflammation (39). Recent studies in mice revealed that a combined deficiency of DNase 1 and DNase1L3 leads to a clotting of vessels by NETs in a disease resembling thrombotic microangiopathies (40). …”

Section: How Cells Die Determines Non-inflammatory Versus Inflammatormentioning

confidence: 99%

Review: Cell Death, Nucleic Acids, and Immunity

Elkon

2018

Arthritis & Rheumatology

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Cells of the innate immune system are rigged with sensors that detect nucleic acids derived from microbes, especially viruses. It has become clear that these same sensors that respond to nucleic acids derived from damaged cells or defective intracellular processing are implicated in triggering diseases such as lupus and arthritis. The ways in which cells die and the concomitant presence of proteins and peptides that allow nucleic acids to re-enter cells profoundly influence innate immune responses. In this review, we briefly discusses different types of programmed necrosis, such as pyroptosis, necroptosis, and NETosis, and explains how nucleic acids can engage intracellular receptors and stimulate inflammation. Host protective mechanisms that include compartmentalization of receptors and nucleases as well as the consequences of nuclease deficiencies are explored. In addition, proximal and distal targets in the nucleic acid stimulation of inflammation are discussed in terms of their potential amenability to therapy for the attenuation of innate immune activation and disease pathogenesis.

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“…Of the four members of the DNASE1 family of extracellular DNases, DNASE1 and DNASE1L3 are responsible for nearly all DNase activity in circulation [46,47]. DNASE1 is primarily expressed in the kidneys and gastrointestinal tract, where it helps digest DNA in food.…”

Section: Dna As An Antigen: Origin and Physical Formmentioning

confidence: 99%

DNA as a self-antigen: nature and regulation

Soni

Reizis

2018

Current Opinion in Immunology

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High-affinity antibodies to double-stranded DNA are a hallmark of systemic lupus erythematosus (SLE) and are thought to contribute to disease flares and tissue inflammation such as nephritis. Notwithstanding their clinical importance, major questions remain about the development and regulation of these pathogenic anti- NA responses. These include the mechanisms that prevent anti-DNA responses in healthy subjects, despite the constant generation of self-DNA and the abundance of DNA-reactive B cells; the nature and physical form of antigenic DNA in SLE; the regulation of DNA availability as an antigen; and potential therapeutic strategies targeting the pathogenic DNA in SLE. This review summarizes current progress in these directions, focusing on the role of secreted DNases in the regulation of antigenic extracellular DNA.

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Host DNases prevent vascular occlusion by neutrophil extracellular traps

Cited by 473 publications

References 29 publications

Neutrophil Extracellular Traps in the Second Decade

Neutrophil Extracellular Traps in the Second Decade

Review: Cell Death, Nucleic Acids, and Immunity

DNA as a self-antigen: nature and regulation

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