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

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Listed:
  • Krishnan MohanKumar

    (University of South Florida
    Johns Hopkins University)

  • Kopperuncholan Namachivayam

    (University of South Florida
    Johns Hopkins University)

  • Tanjing Song

    (University of South Florida)

  • Byeong Jake Cha

    (University of South Florida)

  • Andrea Slate

    (University of South Florida
    Massachusetts General Hospital)

  • Jeanne E. Hendrickson

    (Yale School of Medicine
    Yale School of Medicine)

  • Hua Pan

    (University of South Florida)

  • Samuel A. Wickline

    (University of South Florida)

  • Joo-Yeun Oh

    (University of Alabama at Birmingham)

  • Rakesh P. Patel

    (University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Ling He

    (Johns Hopkins University)

  • Benjamin A. Torres

    (University of South Florida)

  • Akhil Maheshwari

    (University of South Florida
    Johns Hopkins University)

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.

Suggested Citation

  • 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 & Ben, 2019. "A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11199-5
    DOI: 10.1038/s41467-019-11199-5
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