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

Nature Communications
Krishnan MohanKumarAkhil Maheshwari

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.

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Citations

Apr 21, 2020·Frontiers in Immunology·Shiloh R Lueschow, Steven J McElroy
May 6, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kopperuncholan NamachivayamAkhil Maheshwari
Feb 25, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Krishnan MohanKumarAkhil Maheshwari
Jul 1, 2020·Pediatric Research·Akhil Maheshwari
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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
flow cytometry
fluorescence microscopy
nuclear translocation
Fluorescence
PCR

Software Mentioned

PERMANOVA
GraphPad Prism
Beacon Design
Excel
FlowJo

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Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

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