1. A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions
- Author
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Krishnan MohanKumar, Rakesh P. Patel, Jeanne E. Hendrickson, Benjamin A. Torres, Samuel A. Wickline, Tanjing Song, Byeong J. Cha, Joo Yeun Oh, Hua Pan, Kopperuncholan Namachivayam, Andrea R Slate, Akhil Maheshwari, and Ling He
- Subjects
0301 basic medicine ,Necrosis ,General Physics and Astronomy ,02 engineering and technology ,Gastroenterology ,Infant, Newborn, Diseases ,Mice ,Intestinal Mucosa ,lcsh:Science ,Cecum ,Innate immunity ,Enterocolitis ,Multidisciplinary ,biology ,Haptoglobin ,Anemia ,021001 nanoscience & nanotechnology ,3. Good health ,medicine.anatomical_structure ,Necrotizing enterocolitis ,medicine.symptom ,Erythrocyte Transfusion ,0210 nano-technology ,Infant, Premature ,medicine.medical_specialty ,Colon ,Science ,Inflammation ,Paediatric research ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Enterocolitis, Necrotizing ,Ileum ,Internal medicine ,medicine ,Animals ,Humans ,Lamina propria ,business.industry ,Macrophages ,Infant, Newborn ,General Chemistry ,medicine.disease ,digestive system diseases ,Toll-Like Receptor 4 ,Disease Models, Animal ,Red blood cell ,030104 developmental biology ,Animals, Newborn ,biology.protein ,lcsh:Q ,business - 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., The development of neonatal necrotising enterocolitis has been temporally associated with red blood cell transfusions in retrospective human studies. Here, the authors develop a neonatal mouse model of necrotising enterocolitis in anaemic mice receiving red blood cell transfusion that recapitulates features of the human condition.
- Published
- 2019