The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI
Open accessAbstract
Severe AKI is often associated with multiorgan dysfunction, but the mechanisms of this remote tissue injury are unknown. We hypothesized that renal necroinflammation releases cytotoxic molecules that may cause remote organ damage. In hypoxia-induced tubular epithelial cell necrosis in vitro , histone secretion from ischemic tubular cells primed neutrophils to form neutrophil extracellular traps. These traps induced tubular epithelial cell death and stimulated neutrophil extracellular trap formation in fresh neutrophils. In vivo , ischemia-reperfusion injury in the mouse kidney induced tubular necrosis, which preceded the expansion of localized and circulating neutrophil extracellular traps and the increased expression of inflammatory and injury-related genes. Pretreatment with inhibitors of neutrophil extracellular trap formation reduced kidney injury. Dual inhibition of neutrophil trap formation and tubular cell necrosis had an additive protective effect. Moreover, pretreatment with antihistone IgG suppressed ischemia-induced neutrophil extracellular trap formation and renal injury. Renal ischemic injury also increased the levels of circulating histones, and we detected neutrophil infiltration and TUNEL-positive cells in the lungs, liver, brain, and heart along with neutrophil extracellular trap accumulation in the lungs. Inhibition of neutrophil extracellular trap formation or of circulating histones reduced these effects as well. These data suggest that tubular necrosis and neutrophil extracellular trap formation accelerate kidney damage and remote organ dysfunction through cytokine and histone release and identify novel molecular targets to limit renal necroinflammation and multiorgan failure.
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Cites
Neutrophil Extracellular Traps Kill Bacteria
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Novel cell death program leads to neutrophil extracellular traps
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Diabetes primes neutrophils to undergo NETosis, which impairs wound healing
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Self-citationPathophysiology of ischemic acute kidney injury
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Cited by
Targeting potential drivers of COVID-19: Neutrophil extracellular traps
Barnes, B. J., Adrover, J. M., Baxter-Stoltzfus, A., Borczuk, A., Cools-Lartigue, J., Crawford, J. M., Daßler-Plenker, J., Guerci, P., Huynh, C., Knight, J. S., et al. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20200652 · Cited by 1,486
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Calzavacca, P., Licari, E., & Bellomo, R. (2010) · Surgical Intensive Care Medicine · doi:10.1007/978-0-387-77893-8_38 · Cited by 533
Huang, S. U.-S., & O’Sullivan, K. M. (2022) · doi:10.20944/preprints202203.0021.v1 · Cited by 65
Metadata
- Authors
- Nakazawa, D., Kumar, S. V., Marschner, J., Desai, J., Holderied, A., Rath, L., Kraft, F., Lei, Y., Fukasawa, Y., Moeckel, G. W., Angelotti, M. L., Liapis, H., & Anders, H.-J.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2017-01-10
- Volume
- 28
- Issue
- 6
- Pages
- 1753-1768
- ISSN
- 1046-6673 (ISSN-L)
- 1533-3450
- OpenAlex
- W2570320605
- Cited by
- 359
- References
- 41
- FWCI
- 19.20
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI. https://app.cochat.ai/papers/10.1681/asn.2016080925
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- Nakazawa, D., Kumar, S. V., Marschner, J., Desai, J., Holderied, A., Rath, L., Kraft, F., Lei, Y., Fukasawa, Y., Moeckel, G. W., Angelotti, M. L., Liapis, H., & Anders, H.-J. (2017). Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI. Journal of the American Society of Nephrology. https://doi.org/10.1681/asn.2016080925
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