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  • Gardenier, Jason C.Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)

Diphtheria toxin-mediated ablation of lymphatic endothelial cells results in progressive lymphedema

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • American Society for Clinical Investigation,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-310029
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-310029URI
  • https://doi.org/10.1172/jci.insight.84095DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Development of novel treatments for lymphedema has been limited by the fact that the pathophysiology of this disease is poorly understood. It remains unknown, for example, why limb swelling resulting from surgical injury resolves initially, but recurs in some cases months or years later. Finding answers for these basic questions has been hampered by the lack of adequate animal models. In the current study, we used Cre-lox mice that expressed the human diphtheria toxin receptor (DTR) driven by a lymphatic-specific promoter in order to noninvasively ablate the lymphatic system of the hind limb. Animals treated in this manner developed lymphedema that was indistinguishable from clinical lymphedema temporally, radiographically, and histologically. Using this model and clinical biopsy specimens, we show that the initial resolution of edema after injury is dependent on the formation of collateral capillary lymphatics and that this process is regulated by M2-polarized macrophages. In addition, we show that despite these initial improvements in lymphatic function, persistent accumulation of CD4(+) cells inhibits lymphangiogenesis and promotes sclerosis of collecting lymphatics, resulting in late onset of edema and fibrosis. Our findings therefore provide strong evidence that inflammatory changes after lymphatic injury play a key role in the pathophysiology of lymphedema.

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  • Hespe, Geoffrey E.Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)
  • Kataru, Raghu P.Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)
  • Savetsky, Ira L.Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)
  • Torrisi, Jeremy S.Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)
  • Nores, Gabriela D. GarciaMem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)
  • Dayan, Joseph J.Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)
  • Chang, DavidUniv Chicago Med & Biol Sci, Sect Plast & Reconstruct Surg, Chicago, IL USA. (author)
  • Zampell, JamieMem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)
  • Martinez-Corral, InesUppsala universitet,Vaskulärbiologi(Swepub:uu)inema117 (author)
  • Ortega, SagrarioSpanish Natl Canc Res Ctr CNIO, Transgen Mice Unit, Biotechnol Programme, Madrid, Spain. (author)
  • Mehrara, Babak J.Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA. (author)
  • Mem Sloan Kettering Canc Ctr, Dept Surg, Div Plast & Reconstruct Surg, 1275 York Ave, New York, NY 10021 USA.Univ Chicago Med & Biol Sci, Sect Plast & Reconstruct Surg, Chicago, IL USA. (creator_code:org_t)

Related titles

  • In:JCI INSIGHT: American Society for Clinical Investigation1:152379-3708

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