Acetylated Histones in Apoptotic Microparticles Drive the Formation of Neutrophil Extracellular Traps in Active Lupus Nephritis

Rother, Nils; Pieterse, Elmar; Lubbers, J.M.; Hilbrands, Luuk B.; Vlag, Johan van der

doi:10.3389/fimmu.2017.01136

Cited by 60 publications

(57 citation statements)

References 51 publications

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“…Importantly, MPs which contain hyperacetylated histone are more potent than MPs low in hyperacetylated chromatin. As hyperacetylated histones occur during apoptosis, these findings suggest that the function of MPs may vary by molecular composition and setting of particle release …”

Section: The Role Of Microparticles In Slementioning

confidence: 96%

“…Not unexpectedly, MPs contain histones which interact with DNA to form the nucleosome, which are also targeted by autoantibodies in SLE. The presence of histone acetylation can identify the origin of MPs as a consequence of apoptosis since this modification occurs during that process …”

Section: Content Of Nuclear Molecules In Microparticlesmentioning

confidence: 99%

“…In another functional activity, MPs can interact with neutrophils to induce the expression of neutrophil extracellular traps (NETs). NETs are formed in stimulated neutrophils by mixing of chromatin with the content of granules to produce an extended structure . NETS have anti‐bacterial properties but can also damage endothelium.…”

Section: The Role Of Microparticles In Slementioning

confidence: 99%

“…The presence of histone acetylation can identify the origin of MPs as a consequence of apoptosis since this modification occurs during that process. 24,25 The amount of nucleic acid in MPs reflects the amount that is loaded or translocated into the particles as well as the amount undergoing nucleolytic degradation once MPs are in the blood. An enzyme called DNase 1 like 3 (DNase 1L3) may be particularly important for digestion of DNA in the form of MPs.…”

Section: Molecules In Microparticlesmentioning

confidence: 99%

“…NETs are formed in stimulated neutrophils by mixing of chromatin with the content of granules to produce an extended structure. 25 NETS have anti-bacterial properties but can also damage endothelium. As described by Rother et al, MPs prepared from blood of patients with active lupus nephritis can potently induce NETosis.…”

Section: Microparticles In Slementioning

confidence: 99%

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Microparticles as autoantigens in systemic lupus erythematosus

Mobarrez

Svenungsson

Pisetsky

2018

Eur J Clin Investigation

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Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of antibodies to components of the cell nucleus (antinuclear antibodies or ANAs) and the formation of immune complexes with nuclear antigens. These complexes can drive pathogenesis by depositing in the tissue to incite inflammation or induce cytokine production by cells of the innate immune system. While ANAs can bind to purified nuclear molecules, nuclear autoantigens in vivo most likely exist attached to other molecules or embedded in larger structures. Among these structures, microparticles (MPs) are membrane bound vesicles that are released from dead and dying cells by a blebbing process; MPs can also be released during activation of platelets. The presence of MPs in the blood or tissue culture media can be assayed by flow cytometry on the basis of light scattering as well as binding of marker antibodies to identify the cell of origin. As shown by biochemical analyses, MPs contain an ensemble of intracellular components including nuclear, cytoplasmic and membrane molecules. Because of the display of these molecules on the particle surface or in an otherwise accessible form, ANAs, including anti-DNA, can bind to particles. Levels of MPs are increased in the blood of patients with SLE, with flow cytometry demonstrating the presence of IgG-containing particles. In addition to forming immune complexes, MPs can directly stimulate immune responses. Together, these findings suggest an important role of particles in the pathogenesis of SLE and their utility as biomarkers.

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Section: The Role Of Microparticles In Slementioning

confidence: 96%

Section: Content Of Nuclear Molecules In Microparticlesmentioning

confidence: 99%

Section: The Role Of Microparticles In Slementioning

confidence: 99%

Section: Molecules In Microparticlesmentioning

confidence: 99%

Section: Microparticles In Slementioning

confidence: 99%

See 3 more Smart Citations

Microparticles as autoantigens in systemic lupus erythematosus

Mobarrez

Svenungsson

Pisetsky

2018

Eur J Clin Investigation

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Extracellular vesicles arising from apoptosis: forms, functions, and applications

Gregory

Rimmer

2023

The Journal of Pathology

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Extracellular vesicles (EVs) are lipid bilayer‐enclosed subcellular bodies produced by most, if not all cells. Research over the last two decades has recognised the importance of EVs in intercellular communication and horizontal transfer of biological material. EVs range in diameter from tens of nanometres up to several micrometres and are able to transfer a spectrum of biologically active cargoes – from whole organelles, through macromolecules including nucleic acids and proteins, to metabolites and small molecules – from their cells of origin to recipient cells, which may consequently become physiologically or pathologically altered. Based on their modes of biogenesis, the most renowned EV classes are (1) microvesicles, (2) exosomes (both produced by healthy cells), and (3) EVs from cells undergoing regulated death by apoptosis (ApoEVs). Microvesicles bud directly from the plasma membrane, while exosomes are derived from endosomal compartments. Current knowledge of the formation and functional properties of ApoEVs lags behind that of microvesicles and exosomes, but burgeoning evidence indicates that ApoEVs carry manifold cargoes, including mitochondria, ribosomes, DNA, RNAs, and proteins, and perform diverse functions in health and disease. Here we review this evidence, which demonstrates substantial diversity in the luminal and surface membrane cargoes of ApoEVs, permitted by their very broad size range (from around 50 nm to >5 μm; the larger often termed apoptotic bodies), strongly suggests their origins through both microvesicle‐ and exosome‐like biogenesis pathways, and indicates routes through which they interact with recipient cells. We discuss the capacity of ApoEVs to recycle cargoes and modulate inflammatory, immunological, and cell fate programmes in normal physiology and in pathological scenarios such as cancer and atherosclerosis. Finally, we provide a perspective on clinical applications of ApoEVs in diagnostics and therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Unveiling the nexus: Decoding interactions between regulated cell death and systemic lupus erythematosus pathogenesis for innovative therapeutic avenues

Tan,

Huang,

Zheng

et al. 2024

Rheumatology & Autoimmunity

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Systemic lupus erythematosus (SLE) is characterized by disruptions in cell death pathways and impaired clearance of apoptotic cells, resulting in immune dysregulation and tissue damage. This review explores the complex interplay of regulated cell death (RCD) mechanisms, including apoptosis, necroptosis, pyroptosis, NETosis, autophagy, and ferroptosis, in the pathogenesis of SLE. These pathways release autoantigens and danger signals, triggering autoimmune reactions and inflammation. Six various RCDs have mutual associates to support immune dysregulation and are associated with SLE. Apoptosis intrinsically induces immune tolerance by packaging dying cells into immunologically inert fragments. Deficiencies in apoptotic clearance will result in impaired tolerance. Necroptosis, pyroptosis, NETosis, and ferroptosis lead to cell membrane destruction, production of intracellular immunostimulatory components, and triggering a strong inflammatory immune reaction. Abnormal autophagic activity affects the development, differentiation, function, and metabolism of many immune cell subpopulations. Investigating the interconnections between cell death pathways and SLE sheds light on the disease's underlying mechanisms and provides opportunities for novel therapeutic interventions. The convergence of precision medicine and innovative strategies targeting these intricate pathways holds promise for expanding the landscape of SLE treatment.

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Acetylated Histones in Apoptotic Microparticles Drive the Formation of Neutrophil Extracellular Traps in Active Lupus Nephritis

Cited by 60 publications

References 51 publications

Microparticles as autoantigens in systemic lupus erythematosus

Microparticles as autoantigens in systemic lupus erythematosus

Extracellular vesicles arising from apoptosis: forms, functions, and applications

Unveiling the nexus: Decoding interactions between regulated cell death and systemic lupus erythematosus pathogenesis for innovative therapeutic avenues

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