A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions.
Anemia
/ complications
Animals
Animals, Newborn
Cecum
/ pathology
Colon
/ pathology
Disease Models, Animal
Enterocolitis, Necrotizing
/ etiology
Erythrocyte Transfusion
/ adverse effects
Humans
Ileum
/ pathology
Infant, Newborn
Infant, Newborn, Diseases
/ etiology
Infant, Premature
Intestinal Mucosa
/ pathology
Macrophages
/ immunology
Mice
Toll-Like Receptor 4
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 08 2019
02 08 2019
Historique:
received:
19
03
2018
accepted:
27
06
2019
entrez:
4
8
2019
pubmed:
4
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31375667
doi: 10.1038/s41467-019-11199-5
pii: 10.1038/s41467-019-11199-5
pmc: PMC6677753
doi:
Substances chimiques
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3494Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL124078
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107641
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120309
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133022
Pays : United States
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