Autophagocytosis of the apical membrane in microvillus inclusion disease

TY - JOUR

T1 - Autophagocytosis of the apical membrane in microvillus inclusion disease

AU - Reinshagen, K

AU - Naim, H Y

AU - Zimmer, K-P

PY - 2002/10

Y1 - 2002/10

N2 - 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.AIM: This study was performed to define possible alterations of the cytoskeleton and exocytic as well as endocytic pathways within enterocytes in MID.PATIENTS: 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.CONCLUSION: Microvillus inclusion bodies in MID originate from autophagocytosis of the apical membrane of enterocytes with engulfing of microvilli.

AB - 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.AIM: This study was performed to define possible alterations of the cytoskeleton and exocytic as well as endocytic pathways within enterocytes in MID.PATIENTS: 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.CONCLUSION: Microvillus inclusion bodies in MID originate from autophagocytosis of the apical membrane of enterocytes with engulfing of microvilli.

KW - Actins/analysis

KW - Autophagy/physiology

KW - Biopsy

KW - Carrier Proteins/analysis

KW - Cytomegalovirus Infections/metabolism

KW - Cytoskeleton/metabolism

KW - Diarrhea/metabolism

KW - Duodenum/metabolism

KW - Enterocytes/metabolism

KW - Female

KW - Humans

KW - Infant

KW - Male

KW - Microfilament Proteins/analysis

KW - Microscopy, Immunoelectron

KW - Microvilli/metabolism

U2 - 10.1136/gut.51.4.514

DO - 10.1136/gut.51.4.514

M3 - SCORING: Journal article

C2 - 12235073

VL - 51

SP - 514

EP - 521

JO - GUT

JF - GUT

SN - 0017-5749

IS - 4

ER -