title: Blood vessels of human islets of Langerhans are surrounded by a double basement membrane.
abstract: OBJECTIVE
  Based on mouse study findings, pancreatic islet cells are supposed to lack basement membrane (BM) and interact directly with vascular endothelial BM. Until now, the BM composition of human islets has remained elusive.
  
  
  METHODS
  Immunohistochemistry with specific monoclonal and polyclonal antibodies as well as electron microscopy were used to study BM organisation and composition in human adult islets. Isolated islet cells and function-blocking monoclonal antibodies and recombinant soluble Lutheran peptide were further used to study islet cell adhesion to laminin (Lm)-511. Short-term cultures of islets were used to study Lutheran and integrin distribution.
  
  
  RESULTS
  Immunohistochemistry revealed a unique organisation for human Lm-511/521 as a peri-islet BM, which co-invaginated into islets with vessels, forming an outer endocrine BM of the intra-islet vascular channels, and was distinct from the vascular BM that additionally contained Lm-411/421. These findings were verified by electron microscopy. Lutheran glycoprotein, a receptor for the Lm alpha5 chain, was found prominently on endocrine cells, as identified by immunohistochemistry and RT-PCR, whereas alpha(3) and beta(1) integrins were more diffusely distributed. High Lutheran content was also found on endocrine cell membranes in short-term culture of human islets. The adhesion of dispersed beta cells to Lm-511 was inhibited equally effectively by antibodies to integrin and alpha(3) and beta(1) subunits, and by soluble Lutheran peptide.
  
  
  CONCLUSIONS
  The present results disclose a hitherto unrecognised BM organisation and adhesion mechanisms in human pancreatic islets as distinct from mouse islets.
authors.affiliation: Institute of Biomedicine/Anatomy, University of Helsinki, 00014, Helsinki, Finland. ismo.virtanen@helsinki.fi
authors.forename: I
authors.initials: I
authors.lastname: Virtanen
authors.forename: M
authors.initials: M
authors.lastname: Banerjee
authors.forename: J
authors.initials: J
authors.lastname: Palgi
authors.forename: O
authors.initials: O
authors.lastname: Korsgren
authors.forename: A
authors.initials: A
authors.lastname: Lukinius
authors.forename: L-E
authors.initials: LE
authors.lastname: Thornell
authors.forename: Y
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: K
authors.initials: K
authors.lastname: Sekiguchi
authors.forename: M
authors.initials: M
authors.lastname: Hukkanen
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: T
authors.initials: T
authors.lastname: Otonkoski
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D004703:Endocrine System / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000098:blood supply* / Q000166:cytology* / Q000648:ultrastructure; D007797:Laminin / Q000276:immunology / Q000378:metabolism; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D017474:Receptors, Laminin / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C090228:BCAM protein, human; C477645:Bcam protein, mouse; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D007797:Laminin; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D017474:Receptors, Laminin; C097043:laminin alpha5