A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions

Krishnan MohanKumar, Kopperuncholan Namachivayam, Tanjing Song, Byeong Jake Cha, Andrea Slate, Jeanne E. Hendrickson, Hua Pan, Samuel A. Wickline, Joo Yeun Oh, Rakesh P. Patel, Ling He, Benjamin A. Torres, Akhil Maheshwari

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Abstract

Necrotizing enterocolitis (NEC) is an idiopathic, inflammatory bowel necrosis of premature infants. Clinical studies have linked NEC with antecedent red blood cell (RBC) transfusions, but the underlying mechanisms are unclear. Here we report a neonatal murine model to investigate this association. C57BL/6 mouse pups rendered anemic by timed phlebotomy and then given RBC transfusions develop NEC-like intestinal injury with prominent necrosis, inflammation, and submucosal edema/separation of the lamina propria in the ileocecal region and colon within 12–24 h. The anemic intestine is infiltrated by inflammatory macrophages, which are activated in situ by RBC transfusions via a Toll-like receptor (TLR)-4-mediated mechanism and cause bowel injury. Chelation of RBC degradation products with haptoglobin, absence of TLR4, macrophage depletion, and inhibition of macrophage activation is protective. Intestinal injury worsens with increasing severity and the duration of anemia prior to transfusion, indicating a need for the re-evaluation of current transfusion guidelines for premature infants.

Original languageEnglish (US)
Article number3494
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

MohanKumar, K., Namachivayam, K., Song, T., Jake Cha, B., Slate, A., Hendrickson, J. E., Pan, H., Wickline, S. A., Oh, J. Y., Patel, R. P., He, L., Torres, B. A., & Maheshwari, A. (2019). A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions. Nature communications, 10(1), [3494]. https://doi.org/10.1038/s41467-019-11199-5