title: Three-dimensional organization of fenestrae labyrinths in liver sinusoidal endothelial cells.
abstract: OBJECTIVE
  Liver sinusoidal endothelial cell (LSEC) fenestrae are membrane-bound pores that are grouped in sieve plates and act as a bidirectional guardian in regulating transendothelial liver transport. The high permeability of the endothelial lining is explained by the presence of fenestrae and by various membrane-bound transport vesicles. The question as to whether fenestrae relate to other transport compartments remains unclear and has been debated since their discovery almost 40 years ago.
  
  
  METHODS
  In this study, novel insights concerning the three-dimensional (3D) organization of the fenestrated cytoplasm were built on transmission electron tomographical observations on isolated and cultured whole-mount LSECs. Classical transmission electron microscopy and atomic force microscopy imaging was performed to accumulate cross-correlative structural evidence.
  
  
  CONCLUSIONS
  The data presented here indicate that different arrangements of fenestrae have to be considered: i.e. open fenestrae that lack any structural obstruction mainly located in the thin peripheral cytoplasm and complexes of multifolded fenestrae organized as labyrinth-like structures that are found in the proximity of the perinuclear area. Fenestrae in labyrinths constitute about one-third of the total LSEC porosity. The 3D reconstructions also revealed that coated pits and small membrane-bound vesicles are exclusively interspersed in the non-fenestrated cytoplasmic arms.
authors.affiliation: Australian Key Centre for Microscopy and Microanalysis, The University of Sydney, NSW, Australia. f.braet@usyd.edu.au
authors.forename: Filip
authors.initials: F
authors.lastname: Braet
authors.forename: James
authors.initials: J
authors.lastname: Riches
authors.forename: Willie
authors.initials: W
authors.lastname: Geerts
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Jahn
authors.forename: Eddie
authors.initials: E
authors.lastname: Wisse
authors.forename: Peter
authors.initials: P
authors.lastname: Frederik
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology / Q000648:ultrastructure*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008099:Liver / Q000166:cytology*; D008297:Male; D018625:Microscopy, Atomic Force / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D051381:Rats; D017208:Rats, Wistar