title: Autophagocytosis of the apical membrane in microvillus inclusion disease.
abstract: BACKGROUND
  Microvillus inclusion disease (MID) is a disorder with the clinical signs of intractable diarrhoea in the newborn and infancy. The typical pathological features of the disease are well known whereas the pathophysiology is still unclear.
  
  
  OBJECTIVE
  This study was performed to define possible alterations of the cytoskeleton and exocytic as well as endocytic pathways within enterocytes in MID.
  
  
  METHODS
  Four patients with MID were studied. Three had a congenital onset of diarrhoea and one patient had a late onset form.
  
  
  METHODS
  Thin frozen sections of small bowel biopsies of patients were labelled by antibodies against the cytoskeleton and the brush border enzyme sucrase-isomaltase. The binding sites of the primary antibodies were visualised by immunogold particles in the electron microscope. Biopsies were labelled in organ culture to analyse the biosynthetic and endocytic pathways within the enterocytes.
  
  
  RESULTS
  Labelling with antibodies against actin and villin did not differ significantly in control and patient biopsies. Biosynthetic labelling revealed normal intracellular processing and transport of the brush border enzyme sucrase-isomaltase. Secretory granules in crypt epithelial cells were positive for sucrase-isomaltase, differing in its labelling density between patients. Patient biopsies showed microvillus inclusion bodies which endocytosed cationised ferritin within five minutes after uptake as well as ovalbumin after incubation for 10 minutes. These microvillus inclusion bodies correspond to early endosomes because they lack lysosome associated membrane proteins. Late endosomes and lysosomes containing sucrase-isomaltase did not reveal microvillus-like structures.
  
  
  CONCLUSIONS
  Microvillus inclusion bodies in MID originate from autophagocytosis of the apical membrane of enterocytes with engulfing of microvilli.
authors.affiliation: Abteilung für Kinderchirurgie, Chirurgische Klinik der Ruprecht-Karls-Universität Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Reinshagen
authors.forename: H Y
authors.initials: HY
authors.lastname: Naim
authors.forename: K-P
authors.initials: KP
authors.lastname: Zimmer
mesh_terms: D000199:Actins / Q000032:analysis; D001343:Autophagy / Q000502:physiology*; D001706:Biopsy; D002352:Carrier Proteins / Q000032:analysis; D003586:Cytomegalovirus Infections / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D003967:Diarrhea / Q000378:metabolism / Q000503:physiopathology; D004386:Duodenum / Q000378:metabolism / Q000648:ultrastructure; D020895:Enterocytes / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis; D016253:Microscopy, Immunoelectron; D008871:Microvilli / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; D002352:Carrier Proteins; D008840:Microfilament Proteins; C026615:villin