title: CD36 deficiency impairs the small intestinal barrier and induces subclinical inflammation in mice.
abstract: OBJECTIVE
  CD36 has immuno-metabolic actions and is abundant in the small intestine on epithelial, endothelial and immune cells. We examined the role of CD36 in gut homeostasis using mice null for CD36 (CD36KO) and with CD36 deletion specific to enterocytes (Ent-CD36KO) or endothelial cells (EC-CD36KO).
  
  
  METHODS
  Intestinal morphology was evaluated using immunohistochemistry and electron microscopy (EM). Intestinal inflammation was determined from neutrophil infiltration and expression of cytokines, toll-like receptors and COX-2. Barrier integrity was assessed from circulating lipopolysaccharide (LPS) and dextran administered intragastrically. Epithelial permeability to luminal dextran was visualized using two photon microscopy.
  
  
  RESULTS
  The small intestines of CD36KO mice fed a chow diet showed several abnormalities including extracellular matrix (ECM) accumulation with increased expression of ECM proteins, evidence of neutrophil infiltration, inflammation and compromised barrier function. EM showed shortened desmosomes with decreased desmocollin 2 expression. Systemically, leukocytosis and neutrophilia were present together with 80% reduction of anti-inflammatory Ly6Clowmonocytes. Bone marrow transplants supported the primary contribution of non-hematopoietic cells to the inflammatory phenotype. Specific deletion of endothelial but not of enterocyte CD36 reproduced many of the gut phenotypes of germline CD36KO mice including fibronectin deposition, increased interleukin 6, neutrophil infiltration, desmosome shortening and impaired epithelial barrier function.
  
  
  CONCLUSIONS
  CD36 loss results in chronic neutrophil infiltration of the gut, impairs barrier integrity and systemically causes subclinical inflammation. Endothelial cell CD36 deletion reproduces the major intestinal phenotypes. The findings suggest an important role of the endothelium in etiology of gut inflammation and loss of epithelial barrier integrity.
authors.affiliation: Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Cifarelli
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Stoyan
authors.initials: S
authors.lastname: Ivanov
authors.affiliation: Department of Medicine Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY, USA.
authors.forename: Ni-Huiping
authors.initials: NH
authors.lastname: Son
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Saunders
authors.affiliation: Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Terri A
authors.initials: TA
authors.lastname: Pietka
authors.affiliation: Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Trevor M
authors.initials: TM
authors.lastname: Shew
authors.affiliation: Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshino
authors.affiliation: Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Sinju
authors.initials: S
authors.lastname: Sundaresan
authors.affiliation: Department of Medicine Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Davidson
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY, USA.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Gelman
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Zinselmeyer
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.affiliation: Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
keywords: Neutrophils; collagen; endothelium; fibronectin