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  • Yau, Anthony C. Y.Uppsala universitet,Institutionen för immunologi, genetik och patologi (author)

Inflammation and neutrophil extracellular traps in cerebral cavernous malformation

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-03-25
  • Springer Nature,2022
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-472756
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-472756URI
  • https://doi.org/10.1007/s00018-022-04224-2DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Cerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for the first time the formation of neutrophil extracellular traps (NETs) in rodents and humans with CCM. Through RNA-seq analysis of cerebellum endothelial cells from wild-type mice and mice with an endothelial cell-specific ablation of the Ccm3 gene (Ccm3(iECKO)), we show that endothelial cells from Ccm3(iECKO) mice have an increased expression of inflammation-related genes. These genes encode proinflammatory cytokines and chemokines, as well as adhesion molecules, which promote recruitment of inflammatory and immune cells. Similarly, immunoassays showed elevated levels of these cytokines and chemokines in the cerebellum of the Ccm3(iECKO) mice. Consistently, both flow cytometry and immunofluorescence analysis showed infiltration of different subsets of leukocytes into the CCM lesions. Neutrophils, which are known to fight against infection through different strategies, including the formation of NETs, represented the leukocyte subset within the most pronounced increase in CCM. Here, we detected elevated levels of NETs in the blood and the deposition of NETs in the cerebral cavernomas of Ccm3(iECKO) mice. Degradation of NETs by DNase I treatment improved the vascular barrier. The deposition of NETs in the cavernomas of patients with CCM confirms the clinical relevance of NETs in CCM.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Globisch, Maria A.Uppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)margl506 (author)
  • Onyeogaziri, FavourUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)favon830 (author)
  • Conze, Lei LiuUppsala universitet,Institutionen för cell- och molekylärbiologi(Swepub:uu)leliu102 (author)
  • Smith, Ross O.Uppsala universitet,Science for Life Laboratory, SciLifeLab(Swepub:uu)rossm781 (author)
  • Jauhiainen, SuviUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)suvja782 (author)
  • Corada, MonicaFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy. (author)
  • Orsenigo, FabrizioFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy. (author)
  • Huang, Hua,1986-Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)huahu114 (author)
  • Herre, MelanieUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)melhe672 (author)
  • Olsson, Anna-KarinUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)annaolss (author)
  • Malinverno, MatteoFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy. (author)
  • Sundell, VeronicaUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)versu224 (author)
  • Jahromi, Behnam RezaiUniv Helsinki, Dept Neurosurg, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland. (author)
  • Niemela, MikaUniv Helsinki, Dept Neurosurg, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland. (author)
  • Laakso, AkiUniv Helsinki, Dept Neurosurg, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland. (author)
  • Garlanda, CeciliaHumanitas Univ, Dept Biomed Sci, Milan, Italy.;IRCCS Humanitas Res Hosp, Milan, Italy. (author)
  • Mantovani, AlbertoHumanitas Univ, Dept Biomed Sci, Milan, Italy.;IRCCS Humanitas Res Hosp, Milan, Italy.;Queen Mary Univ London, William Harvey Res Inst, London, England. (author)
  • Lampugnani, Maria GraziaFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.;Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy. (author)
  • Dejana, ElisabettaUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.(Swepub:uu)elide443 (author)
  • Magnusson, PeetraUppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi(Swepub:uu)petrmagn (author)
  • Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

Related titles

  • In:Cellular and Molecular Life Sciences (CMLS): Springer Nature79:41420-682X1420-9071

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