Anemia induces gut inflammation and injury in an animal model of preterm infants.
| Title: | Anemia induces gut inflammation and injury in an animal model of preterm infants. |
|---|---|
| Authors: | Arthur CM; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Nalbant D; Department of Pediatrics, University of Iowa, Iowa City, Iowa.; Feldman HA; Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts.; Saeedi BJ; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Matthews J; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Robinson BS; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Kamili NA; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Bennett A; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Cress GA; Department of Pediatrics, University of Iowa, Iowa City, Iowa.; Sola-Visner M; Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts.; Jones RM; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Zimmerman MB; Department of Pediatrics, University of Iowa, Iowa City, Iowa.; Neish AS; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Patel RM; Pediatrics, Emory University School of Medicine, Atlanta, Georgia.; Nopoulos P; Department of Psychiatry, College of Medicine, University of Iowa, Iowa City, Iowa.; Georgieff MK; Department of Pediatrics, School of Medicine, University of Minnesota, Minneapolis, Minnesota.; Roback JD; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Widness JA; Department of Pediatrics, University of Iowa, Iowa City, Iowa.; Josephson CD; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia.; Pediatrics, Emory University School of Medicine, Atlanta, Georgia.; Stowell SR; Departments of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Atlanta, Georgia. |
| Source: | Transfusion [Transfusion] 2019 Apr; Vol. 59 (4), pp. 1233-1245. Date of Electronic Publication: 2019 Mar 21. |
| Publication Type: | Clinical Trial; Journal Article; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: American Association Of Blood Banks Country of Publication: United States NLM ID: 0417360 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-2995 (Electronic) Linking ISSN: 00411132 NLM ISO Abbreviation: Transfusion Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Arlington, Va. : American Association Of Blood Banks |
| MeSH Terms: | Anemia*/complications ; Anemia*/metabolism ; Anemia*/pathology ; Enterocolitis, Necrotizing*/etiology ; Enterocolitis, Necrotizing*/metabolism ; Enterocolitis, Necrotizing*/pathology ; Intestinal Mucosa*/metabolism ; Intestinal Mucosa*/pathology ; Infant, Premature* ; Infant, Premature, Diseases* ; Infant, Very Low Birth Weight*; Inflammation/etiology ; Inflammation/metabolism ; Inflammation/pathology ; Interferon-gamma/metabolism ; Zonula Occludens-1 Protein/metabolism ; Animals ; Disease Models, Animal ; Female ; Humans ; Infant, Newborn ; Male ; Mice |
| Abstract: | Background: While very low birth weight (VLBW) infants often require multiple red blood cell transfusions, efforts to minimize transfusion-associated risks have resulted in more restrictive neonatal transfusion practices. However, whether restrictive transfusion strategies limit transfusions without increasing morbidity and mortality in this population remains unclear. Recent epidemiologic studies suggest that severe anemia may be an important risk factor for the development of necrotizing enterocolitis (NEC). However, the mechanism whereby anemia may lead to NEC remains unknown.; Study Design and Methods: The potential impact of anemia on neonatal inflammation and intestinal barrier disruption, two well-characterized predisposing features of NEC, was defined by correlation of hemoglobin values to cytokine levels in premature infants and by direct evaluation of intestinal hypoxia, inflammation and gut barrier disruption using a pre-clinical neonatal murine model of phlebotomy-induced anemia (PIA).; Results: Increasing severity of anemia in the preterm infant correlated with the level of IFN-gamma, a key pro-inflammatory cytokine that may predispose an infant to NEC. Gradual induction of PIA in a pre-clinical model resulted in significant hypoxia throughout the intestinal mucosa, including areas where intestinal macrophages reside. PIA-induced hypoxia significantly increased macrophage pro-inflammatory cytokine levels, while reducing tight junction protein ZO-1 expression and increasing intestinal barrier permeability. Macrophage depletion reversed the impact of anemia on intestinal ZO-1 expression and barrier function.; Conclusions: Taken together, these results suggest that anemia can increase intestinal inflammation and barrier disruption likely through altered macrophage function, leading to the type of predisposing intestinal injury that may increase the risk for NEC.; (© 2019 AABB.) |
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| Grant Information: | DP5OD019892 United States NH NIH HHS; P01 HL086773 United States HL NHLBI NIH HHS; R01 HL135575 United States HL NHLBI NIH HHS; R01HL13557501 United States HL NHLBI NIH HHS; DP5 OD019892 United States OD NIH HHS; P01 HL046925 United States HL NHLBI NIH HHS; P01HL04692520 United States HL NHLBI NIH HHS; F31 HL138934 United States HL NHLBI NIH HHS; T32 GM008169 United States GM NIGMS NIH HHS |
| Substance Nomenclature: | 0 (IFNG protein, human); 0 (IFNG protein, mouse); 0 (TJP1 protein, human); 0 (Tjp1 protein, mouse); 0 (Zonula Occludens-1 Protein); 82115-62-6 (Interferon-gamma) |
| Entry Date(s): | Date Created: 20190322 Date Completed: 20200519 Latest Revision: 20260302 |
| Update Code: | 20260302 |
| PubMed Central ID: | PMC6525338 |
| DOI: | 10.1111/trf.15254 |
| PMID: | 30897226 |
| Database: | MEDLINE |
Clinical Trial; Journal Article; Research Support, N.I.H., Extramural