Dual roles for hepatic lectin receptors in the clearance of chilled platelets

TY - JOUR

T1 - Dual roles for hepatic lectin receptors in the clearance of chilled platelets

AU - Rumjantseva, Viktoria

AU - Grewal, Prabhjit K

AU - Wandall, Hans H

AU - Josefsson, Emma C

AU - Sørensen, Anne Louise

AU - Larson, Göran

AU - Marth, Jamey D

AU - Hartwig, John H

AU - Hoffmeister, Karin M

PY - 2009

Y1 - 2009

N2 - Rapid chilling causes glycoprotein-Ib (GPIb) receptors to cluster on blood platelets. Hepatic macrophage beta(2) integrin binding to beta-N-acetylglucosamine (beta-GlcNAc) residues in the clusters leads to rapid clearance of acutely chilled platelets after transfusion. Although capping the beta-GlcNAc moieties by galactosylation prevents clearance of short-term-cooled platelets, this strategy is ineffective after prolonged refrigeration. We report here that prolonged refrigeration increased the density and concentration of exposed galactose residues on platelets such that hepatocytes, through Ashwell-Morell receptor binding, become increasingly involved in platelet removal. Macrophages rapidly removed a large fraction of transfused platelets independent of their storage conditions. With prolonged platelet chilling, hepatocyte-dependent clearance further diminishes platelet recovery and survival after transfusion. Inhibition of chilled platelet clearance by both beta(2) integrin and Ashwell-Morell receptors may afford a potentially simple method for storing platelets in the cold.

AB - Rapid chilling causes glycoprotein-Ib (GPIb) receptors to cluster on blood platelets. Hepatic macrophage beta(2) integrin binding to beta-N-acetylglucosamine (beta-GlcNAc) residues in the clusters leads to rapid clearance of acutely chilled platelets after transfusion. Although capping the beta-GlcNAc moieties by galactosylation prevents clearance of short-term-cooled platelets, this strategy is ineffective after prolonged refrigeration. We report here that prolonged refrigeration increased the density and concentration of exposed galactose residues on platelets such that hepatocytes, through Ashwell-Morell receptor binding, become increasingly involved in platelet removal. Macrophages rapidly removed a large fraction of transfused platelets independent of their storage conditions. With prolonged platelet chilling, hepatocyte-dependent clearance further diminishes platelet recovery and survival after transfusion. Inhibition of chilled platelet clearance by both beta(2) integrin and Ashwell-Morell receptors may afford a potentially simple method for storing platelets in the cold.

U2 - 10.1038/nm.2030

DO - 10.1038/nm.2030

M3 - Journal article

C2 - 19783995

SN - 1078-8956

VL - 15

SP - 1273

EP - 1280

JO - Nature Medicine

JF - Nature Medicine

IS - 11

ER -