PMID- 18063704
OWN - NLM
STAT- MEDLINE
DCOM- 20080325
LR  - 20131121
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 294
IP  - 2
DP  - 2008 Feb
TI  - Liver sinusoidal endothelial cells are the principal site for elimination of 
      unfractionated heparin from the circulation.
PG  - G520-8
AB  - The mechanism of elimination of blood borne heparin was studied. To this end 
      unfractionated heparin (UFH) was tagged with FITC, which served as both a visual 
      marker and a site of labeling with (125)I-iodine. UFH labeled in this manner did 
      not alter the anticoagulant activity or binding specificity of the 
      glycosaminoglycan. Labeled heparin administered intravenously to rats (0.1 IU/kg) 
      had a circulatory t(1/2) of 1.7 min, which was increased to 16 min upon 
      coinjection with unlabeled UFH (100 IU/kg). At 15 min after injection, 71% of 
      recovered radioactivity was found in liver. Liver cell separation revealed the 
      following relative uptake capacity, expressed per cell: liver sinusoidal 
      endothelial cell (LSEC)-parenchymal cell-Kupffer cell = 15:3.6:1. Fluorescence 
      microscopy on liver sections showed accumulation of FITC-UFH only in cells lining 
      the liver sinusoids. No fluorescence was detected in parenchymal cells or 
      endothelial cells lining the central vein. Fluorescence microscopy of cultured 
      LSECs following binding of FITC-UFH at 4 degrees C and chasing at 37 degrees C, 
      showed accumulation of the probe in vesicles located at the periphery of the 
      cells after 10 min, with transfer to large, evenly stained vesicles in the 
      perinuclear region after 2 h. Immunogold electron microscopy of LSECs to probe 
      the presence of FITC following injection of FITC-UFH along with BSA-gold to mark 
      lysosomes demonstrated colocalization of the probe with the gold particles in the 
      lysosomal compartment. Receptor-ligand competition experiments in primary 
      cultures of LSECs indicated the presence of a specific heparin receptor, 
      functionally distinct from the hyaluronan/scavenger receptor (Stabilin2). The 
      results suggest a major role for LSECs in heparin elimination.
FAU - Oie, Cristina Ionica
AU  - Oie CI
AD  - Center for Atherothrombotic Research in Tromso, Department of Medicine, Institute 
      of Clinical Medicine, University of Tromso, N-9037 Tromso, Norway. 
      cristina@fagmed.uit.no
FAU - Olsen, Randi
AU  - Olsen R
FAU - Smedsrod, Bard
AU  - Smedsrod B
FAU - Hansen, John-Bjarne
AU  - Hansen JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071206
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Anticoagulants)
RN  - 0 (Fluorescent Dyes)
RN  - 9005-49-6 (Heparin)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Animals
MH  - Anticoagulants/blood/*metabolism
MH  - Biological Transport, Active
MH  - Endocytosis/physiology
MH  - Epithelial Cells/*metabolism/ultrastructure
MH  - Fluorescein-5-isothiocyanate
MH  - Fluorescent Dyes
MH  - Heparin/blood/*metabolism
MH  - Hepatocytes/*metabolism/ultrastructure
MH  - Immunohistochemistry
MH  - Male
MH  - Microscopy, Electron
MH  - Microscopy, Fluorescence
MH  - Microscopy, Phase-Contrast
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tissue Distribution
EDAT- 2007/12/08 09:00
MHDA- 2008/03/26 09:00
CRDT- 2007/12/08 09:00
PHST- 2007/12/08 09:00 [pubmed]
PHST- 2008/03/26 09:00 [medline]
PHST- 2007/12/08 09:00 [entrez]
AID - 00489.2007 [pii]
AID - 10.1152/ajpgi.00489.2007 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2008 Feb;294(2):G520-8. doi: 
      10.1152/ajpgi.00489.2007. Epub 2007 Dec 6.