HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/G520    most recent 00489.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Øie, C. I. Articles by Hansen, J.-B. Search for Related Content PubMed PubMed Citation Articles by Øie, C. I. Articles by Hansen, J.-B.

LIVER AND BILIARY TRACT

Liver sinusoidal endothelial cells are the principal site for elimination of unfractionated heparin from the circulation

¹Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine; ²Department of Electron Microscopy, Faculty of Medicine; ³Department of Cell Biology and Histology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway

Submitted 25 October 2007 ; accepted in final form 4 December 2007

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 ¹²⁵I-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°C and chasing at 37°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.

clearance; receptor-mediated endocytosis; fluorescence microscopy

This article has been cited by other articles:

				E. N. Harris, B. A. Baggenstoss, and P. H. Weigel Rat and human HARE/stabilin-2 are clearance receptors for high- and low-molecular-weight heparins Am J Physiol Gastrointest Liver Physiol, June 1, 2009; 296(6): G1191 - G1199. [Abstract] [Full Text] [PDF]