title: Molecular composition of the peri-islet basement membrane in NOD mice: a barrier against destructive insulitis.
abstract: OBJECTIVE
  This study examined whether the capsule which encases islets of Langerhans in the NOD mouse pancreas represents a specialised extracellular matrix (ECM) or basement membrane that protects islets from autoimmune attack.
  
  
  METHODS
  Immunofluorescence microscopy using a panel of antibodies to collagens type IV, laminins, nidogens and perlecan was performed to localise matrix components in NOD mouse pancreas before diabetes onset, at onset of diabetes and after clinical diabetes was established (2-8.5 weeks post-onset).
  
  
  RESULTS
  Perlecan, a heparan sulphate proteoglycan that is characteristic of basement membranes and has not previously been investigated in islets, was localised in the peri-islet capsule and surrounding intra-islet capillaries. Other components present in the peri-islet capsule included laminin chains alpha2, beta1 and gamma1, collagen type IV alpha1 and alpha2, and nidogen 1 and 2. Collagen type IV alpha3-alpha6 were not detected. These findings confirm that the peri-islet capsule represents a specialised ECM or conventional basement membrane. The islet basement membrane was destroyed in islets where intra-islet infiltration of leucocytes marked the progression from non-destructive to destructive insulitis. No changes in basement membrane composition were observed before leucocyte infiltration.
  
  
  CONCLUSIONS
  These findings suggest that the islet basement membrane functions as a physical barrier to leucocyte migration into islets and that degradation of the islet basement membrane marks the onset of destructive autoimmune insulitis and diabetes development in NOD mice. The components of the islet basement membrane that we identified predict that specialised degradative enzymes are likely to function in autoimmune islet damage.
authors.affiliation: Research Centre for Reproductive Health, Department of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: H F
authors.initials: HF
authors.lastname: Irving-Rodgers
authors.forename: A F
authors.initials: AF
authors.lastname: Ziolkowski
authors.forename: C R
authors.initials: CR
authors.lastname: Parish
authors.forename: Y
authors.initials: Y
authors.lastname: Sado
authors.forename: Y
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: C J
authors.initials: CJ
authors.lastname: Simeonovic
authors.forename: R J
authors.initials: RJ
authors.lastname: Rodgers
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D011236:Prediabetic State / Q000473:pathology; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D024141:Collagen Type IV; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan