Matches in SemOpenAlex for { <https://semopenalex.org/work/W2948037350> ?p ?o ?g. }
- W2948037350 abstract "Abstract Neutrophil extracellular traps (NETs) are web-like DNA structures decorated with histones and cytotoxic proteins that are released by activated neutrophils to trap and neutralize pathogens during the innate immune response, but also form in and exacerbate sterile inflammation. Peptidylarginine deiminase 4 (PAD4) citrullinates histones and is required for NET formation (NETosis) in mouse neutrophils. While the in vivo impact of NETs is accumulating, the cellular events driving NETosis and the role of PAD4 in these events are unclear. We performed high resolution time-lapse microscopy of mouse and human neutrophils (PMN) and differentiated HL-60 neutrophil-like cells (dHL-60) labelled with fluorescent markers of organelles and stimulated with ionomycin or lipopolysaccharides to induce NETosis. Upon stimulation, cells exhibited rapid disassembly of the actin cytoskeleton, followed by shedding of plasma membrane microvesicles, disassembly and remodeling of the microtubule and vimentin cytoskeletons, ER vesiculation, chromatin de-condensation and nuclear rounding, progressive plasma membrane and nuclear envelope (NE) permeabilization, nuclear lamin meshwork and then NE rupture to release DNA into the cytoplasm, and finally plasma membrane rupture and discharge of extracellular DNA. Inhibition of actin disassembly blocked NET release. Mouse and dHL-60 cells bearing genetic alteration of PAD4 showed that chromatin de-condensation, lamin meshwork and NE rupture and extracellular DNA release required the enzymatic and nuclear localization activities of PAD4. Thus, NETosis proceeds by a step-wise sequence of cellular events culminating in the PAD4-mediated expulsion of DNA. Significance Statement Neutrophils are white blood cells specialized as the first line of host defense in the immune system. One way they protect organisms is through NETosis, in which they expel their DNA to form a web-like trap that ensnares pathogens and promotes clotting. However, NETs also mediate sterile inflammation, causing damage to the body. We used high-resolution live-cell microscopy to perform the first systematic characterization of the timing of dynamic cellular events leading to NETosis in human and mouse neutrophils and a neutrophil-like cell line. We discovered that NETosis proceeds by a step-wise sequence of cellular events that is conserved across species, and requires the activity of the PAD4 enzyme for DNA to be released from the nucleus and cell membrane." @default.
- W2948037350 created "2019-06-14" @default.
- W2948037350 creator A5001030035 @default.
- W2948037350 creator A5004905921 @default.
- W2948037350 creator A5018254854 @default.
- W2948037350 creator A5032584210 @default.
- W2948037350 creator A5049861510 @default.
- W2948037350 creator A5051946237 @default.
- W2948037350 creator A5066880935 @default.
- W2948037350 creator A5076909940 @default.
- W2948037350 creator A5077476585 @default.
- W2948037350 date "2019-06-06" @default.
- W2948037350 modified "2023-09-27" @default.
- W2948037350 title "NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin de-condensation and nuclear envelope rupture" @default.
- W2948037350 cites W14472107 @default.
- W2948037350 cites W1540408159 @default.
- W2948037350 cites W1913879859 @default.
- W2948037350 cites W1963645455 @default.
- W2948037350 cites W1966774641 @default.
- W2948037350 cites W1972779128 @default.
- W2948037350 cites W1974354099 @default.
- W2948037350 cites W1977709885 @default.
- W2948037350 cites W1986282241 @default.
- W2948037350 cites W1986747192 @default.
- W2948037350 cites W1987371172 @default.
- W2948037350 cites W2002846976 @default.
- W2948037350 cites W2006008435 @default.
- W2948037350 cites W2011145349 @default.
- W2948037350 cites W2011491918 @default.
- W2948037350 cites W2014678245 @default.
- W2948037350 cites W2014776493 @default.
- W2948037350 cites W2016283343 @default.
- W2948037350 cites W2016385216 @default.
- W2948037350 cites W2020520526 @default.
- W2948037350 cites W2027238399 @default.
- W2948037350 cites W2027416251 @default.
- W2948037350 cites W2034957971 @default.
- W2948037350 cites W2035052662 @default.
- W2948037350 cites W2045819100 @default.
- W2948037350 cites W2050330325 @default.
- W2948037350 cites W2052090797 @default.
- W2948037350 cites W2053914489 @default.
- W2948037350 cites W2057259507 @default.
- W2948037350 cites W2070117107 @default.
- W2948037350 cites W2070340172 @default.
- W2948037350 cites W2073676586 @default.
- W2948037350 cites W2074966513 @default.
- W2948037350 cites W2075100878 @default.
- W2948037350 cites W2075491335 @default.
- W2948037350 cites W2089782191 @default.
- W2948037350 cites W2094009347 @default.
- W2948037350 cites W2096355575 @default.
- W2948037350 cites W2096696596 @default.
- W2948037350 cites W2104934425 @default.
- W2948037350 cites W2108166850 @default.
- W2948037350 cites W2112543741 @default.
- W2948037350 cites W2114934533 @default.
- W2948037350 cites W2115959782 @default.
- W2948037350 cites W2116316741 @default.
- W2948037350 cites W2118217258 @default.
- W2948037350 cites W2119999870 @default.
- W2948037350 cites W2121134187 @default.
- W2948037350 cites W2125376694 @default.
- W2948037350 cites W2129429248 @default.
- W2948037350 cites W2129725597 @default.
- W2948037350 cites W2135745724 @default.
- W2948037350 cites W2135849676 @default.
- W2948037350 cites W2145392559 @default.
- W2948037350 cites W2152502508 @default.
- W2948037350 cites W2155651511 @default.
- W2948037350 cites W2162159732 @default.
- W2948037350 cites W2164304811 @default.
- W2948037350 cites W2168176302 @default.
- W2948037350 cites W2169067272 @default.
- W2948037350 cites W2308469998 @default.
- W2948037350 cites W2418806051 @default.
- W2948037350 cites W2461915818 @default.
- W2948037350 cites W2462773201 @default.
- W2948037350 cites W2534066964 @default.
- W2948037350 cites W2593144838 @default.
- W2948037350 cites W2600424538 @default.
- W2948037350 cites W2621393405 @default.
- W2948037350 cites W2621491385 @default.
- W2948037350 cites W2738981501 @default.
- W2948037350 cites W2750129063 @default.
- W2948037350 cites W2766814657 @default.
- W2948037350 cites W2766872204 @default.
- W2948037350 cites W2775011307 @default.
- W2948037350 cites W2783882235 @default.
- W2948037350 cites W2802099741 @default.
- W2948037350 cites W2885977543 @default.
- W2948037350 cites W2888168693 @default.
- W2948037350 cites W2888725678 @default.
- W2948037350 cites W2890771157 @default.
- W2948037350 cites W2894451493 @default.
- W2948037350 cites W2897882351 @default.
- W2948037350 cites W2904548584 @default.
- W2948037350 cites W2909520779 @default.
- W2948037350 cites W2954636025 @default.
- W2948037350 cites W2965111812 @default.