scholarly journals Charcot-Leyden crystal formation is closely associated with eosinophil extracellular trap cell death

Blood ◽  
2018 ◽  
Vol 132 (20) ◽  
pp. 2183-2187 ◽  
Author(s):  
Shigeharu Ueki ◽  
Takahiro Tokunaga ◽  
Rossana C. N. Melo ◽  
Hidekazu Saito ◽  
Kohei Honda ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Protein Crystallization ◽  
Intracellular Localization ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Crystal Formation ◽  
Membrane Rupture ◽  
Extracellular Traps ◽  
Extracellular Trap ◽  
Trap Cell

Abstract Protein crystallization in human tissue rarely occurs. Charcot-Leyden crystals (CLCs) were described in various eosinophilic diseases >150 years ago, but our understanding of CLC formation still remains limited. In this study, we demonstrate that CLCs observed in varied inflamed human tissues are closely associated with eosinophil cell-free granules and nuclear envelope/plasma membrane disintegration with release of filamentous chromatin (extracellular traps), typical morphologies of a regulated pathway of extracellular trap cell death (ETosis). During the process of eosinophil ETosis, eccentrically localized cytoplasmic and perinuclear CLC protein (galectin-10) is homogeneously redistributed in the cytoplasm. Rapid (1-2 minutes) formation of intracytoplasmic CLCs was observed using time-lapse imaging. Plasma membrane rupture enabled the release of both intracellularly formed CLCs and soluble galectin-10 that further contributed to formation of CLCs extracellularly, in parallel with the expulsion of free intact granules and extracellular traps. CLC formation and galectin-10 release were dependent on nicotinamide adenine dinucleotide phosphate oxidase activation. To our knowledge, this is the first demonstration of natural formation of CLCs in association with an active physiological process (ie, ETosis). These results indicate that dynamic changes in intracellular localization and release of galectin-10 contribute to CLC formation in vivo and suggest that CLC/galectin-10 might serve as an indicator of ETosis.

scholarly journals The Card19 locus of murine chromosome 13 regulates terminal cell lysis downstream of caspase activation and Gasdermin-D cleavage

2021 ◽  
Author(s):  
Elisabet Bjanes ◽  
Reyna Garcia Sillas ◽  
Rina Matsuda ◽  
Benjamin Demarco ◽  
Timothée Fettrelet ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Cell Lysis ◽  
Terminal Cell ◽  
Snp Analysis ◽  
Caspase Activation ◽  
Chromosome 13 ◽  
Murine Chromosome ◽  
Membrane Rupture ◽  
Yersinia Infection

Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 cytokine release. Terminal cell lysis and IL-1β release following caspase activation can be uncoupled in certain cell types or in response to particular stimuli, a state termed hyperactivation. However, the factors and mechanisms that regulate terminal cell lysis downstream of GSDMD cleavage remain poorly understood. In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19-/- mice whose macrophages were protected from cell death and showed reduced pore formation during apoptosis or pyroptosis, yet had wild-type levels of caspase activation, IL-1 secretion, and GSDMD cleavage. Unexpectedly, CARD19, a mitochondrial CARD-containing protein, was not directly responsible for this, as two independently-generated CRISPR/Cas9 Card19 knockout mice showed no defect in macrophage cell lysis. The original Card19-/- line was generated in a 129SvEvBrd background, and SNP analysis revealed a six megabase region of 129 origin co-segregating with the Card19 locus. Card19 is located on chromosome 13, adjacent to Ninj1, which was recently reported to regulate cell lysis downstream of GSDMD activation. Nonetheless, we could not detect major defects in NINJ1 protein expression or mutations in Ninj1 coding sequence in Card19-/- mice. Mice from the original Card19-/- line exhibited significantly increased susceptibility to Yersinia infection, demonstrating that cell lysis itself plays a key role in protection against bacterial infection. Our findings identify a locus on murine chromosome 13 that regulates the ability of macrophages to undergo plasma membrane rupture downstream of gasdermin cleavage, and implicates additional NINJ1-independent factors that control terminal cell lysis.

scholarly journals Genetic targeting of Card19 is linked to disrupted NINJ1 expression, impaired cell lysis, and increased susceptibility to Yersinia infection

2021 ◽  
Vol 17 (10) ◽  
pp. e1009967
Author(s):  
Elisabet Bjanes ◽  
Reyna Garcia Sillas ◽  
Rina Matsuda ◽  
Benjamin Demarco ◽  
Timothée Fettrelet ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Cell Lysis ◽  
Terminal Cell ◽  
Caspase Activation ◽  
Membrane Rupture ◽  
Genetic Targeting ◽  
Increased Susceptibility

Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 cytokine release. Terminal cell lysis and IL-1β release following caspase activation can be uncoupled in certain cell types or in response to particular stimuli, a state termed hyperactivation. However, the factors and mechanisms that regulate terminal cell lysis downstream of GSDMD cleavage remain poorly understood. In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19-deficient mice (Card19lxcn) whose macrophages were protected from cell lysis and showed reduced apoptosis and pyroptosis, yet had wild-type levels of caspase activation, IL-1 secretion, and GSDMD cleavage. Unexpectedly, CARD19, a mitochondrial CARD-containing protein, was not directly responsible for this, as an independently-generated CRISPR/Cas9 Card19 knockout mouse line (Card19Null) showed no defect in macrophage cell lysis. Notably, Card19 is located on chromosome 13, immediately adjacent to Ninj1, which was recently found to regulate cell lysis downstream of GSDMD activation. RNA-seq and western blotting revealed that Card19lxcn BMDMs have significantly reduced NINJ1 expression, and reconstitution of Ninj1 in Card19lxcn immortalized BMDMs restored their ability to undergo cell lysis in response to caspase-dependent cell death stimuli. Card19lxcn mice exhibited increased susceptibility to Yersinia infection, whereas independently-generated Card19Null mice did not, demonstrating that cell lysis itself plays a key role in protection against bacterial infection, and that the increased infection susceptibility of Card19lxcn mice is attributable to loss of NINJ1. Our findings identify genetic targeting of Card19 being responsible for off-target effects on the adjacent gene Ninj1, disrupting the ability of macrophages to undergo plasma membrane rupture downstream of gasdermin cleavage and impacting host survival and bacterial control during Yersinia infection.

scholarly journals Evidence of eosinophil extracellular trap cell death in COPD: does it represent the trigger that switches on the disease?

2017 ◽  
Vol Volume 12 ◽  
pp. 885-896 ◽  
Author(s):  
Loli Uribe Echevarría ◽  
Carolina Leimgruber ◽  
Jorge García González ◽  
Alberto Nevado ◽  
Ruth Álvarez ◽  
...  
Keyword(s):  
Cell Death ◽  
Extracellular Trap ◽  
Trap Cell

scholarly journals Neutrophil extracellular trap cell death requires both autophagy and superoxide generation

Cell Research ◽  
2010 ◽  
Vol 21 (2) ◽  
pp. 290-304 ◽  
Author(s):  
Quinten Remijsen ◽  
Tom Vanden Berghe ◽  
Ellen Wirawan ◽  
Bob Asselbergh ◽  
Eef Parthoens ◽  
...  
Keyword(s):  
Cell Death ◽  
Neutrophil Extracellular Trap ◽  
Superoxide Generation ◽  
Extracellular Trap ◽  
Trap Cell

IFN-γ Induces Mimic Extracellular Trap Cell Death in Lung Epithelial Cells Through Autophagy-Regulated DNA Damage

2016 ◽  
Vol 36 (2) ◽  
pp. 100-112 ◽  
Author(s):  
Chiou-Feng Lin ◽  
Shun-Yi Chien ◽  
Chia-Ling Chen ◽  
Chia-Yuan Hsieh ◽  
Po-Chun Tseng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Ifn Γ ◽  
Extracellular Trap ◽  
Trap Cell

scholarly journals Eosinophil extracellular trap cell death–derived DNA traps: Their presence in secretions and functional attributes

2016 ◽  
Vol 137 (1) ◽  
pp. 258-267 ◽  
Author(s):  
Shigeharu Ueki ◽  
Yasunori Konno ◽  
Masahide Takeda ◽  
Yuki Moritoki ◽  
Makoto Hirokawa ◽  
...  
Keyword(s):  
Cell Death ◽  
Functional Attributes ◽  
Extracellular Trap ◽  
Trap Cell

Eosinophilic Otitis Media: the Aftermath of Eosinophil Extracellular Trap Cell Death

2017 ◽  
Vol 17 (5) ◽  
Author(s):  
Shigeharu Ueki ◽  
Nobuo Ohta ◽  
Masahide Takeda ◽  
Yasunori Konno ◽  
Makoto Hirokawa
Keyword(s):  
Cell Death ◽  
Otitis Media ◽  
Extracellular Trap ◽  
Trap Cell

scholarly journals Allergic Bronchopulmonary Aspergillosis–A Luminal Hypereosinophilic Disease With Extracellular Trap Cell Death

2018 ◽  
Vol 9 ◽  
Author(s):  
Shigeharu Ueki ◽  
Akira Hebisawa ◽  
Masashi Kitani ◽  
Koichiro Asano ◽  
Josiane S. Neves
Keyword(s):  
Cell Death ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Extracellular Trap ◽  
Trap Cell

scholarly journals Ferroptotic pores induce Ca2+ fluxes and ESCRT-III activation to modulate cell death kinetics

2020 ◽  
Author(s):  
Lohans Pedrera ◽  
Rafael A. Espiritu ◽  
Uris Ros ◽  
Josephine Weber ◽  
Anja Schmitt ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Plasma Membrane ◽  
Membrane Damage ◽  
Protective Mechanism ◽  
Membrane Repair ◽  
Membrane Rupture ◽  
Plasma Membrane Damage ◽  
Regulated Necrosis ◽  
Sustained Increase

AbstractFerroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxidation. Despite its key role in the inflammatory outcome of ferroptosis, little is known about the molecular events leading to the disruption of the plasma membrane during this type of cell death. Here we show that a sustained increase in cytosolic Ca2+ is a hallmark of ferroptosis that precedes complete bursting of the cell. We report that plasma membrane damage leading to ferroptosis is associated with membrane nanopores of a few nanometers in radius and that ferroptosis, but not lipid peroxidation, can be delayed by osmoprotectants. Importantly, Ca2+ fluxes during ferroptosis induce the activation of the ESCRT-III-dependent membrane repair machinery, which counterbalances the kinetics of cell death and modulates the immunological signature of ferroptosis. Our findings with ferroptosis provide a unifying concept that sustained increase of cytosolic Ca2+ prior to plasma membrane rupture is a common feature of regulated types of necrosis and position ESCRT-III activation as a general protective mechanism in these lytic cell death pathways.

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