scholarly journals Endocytic uptake of advanced glycation end products by mouse liver sinusoidal endothelial cells is mediated by a scavenger receptor distinct from the macrophage scavenger receptor class A

2000 ◽  
Vol 352 (1) ◽  
pp. 233-240 ◽  
Author(s):  
Kenshi MATSUMOTO ◽  
Hiroyuki SANO ◽  
Ryoji NAGAI ◽  
Hiroshi SUZUKI ◽  
Tatsuhiko KODAMA ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Peritoneal Macrophages ◽  
Wild Type ◽  
Advanced Glycation ◽  
Liver Sinusoidal Endothelial Cells ◽  
Knock Out ◽  
Class A ◽  
Macrophage Scavenger Receptor ◽  
Scavenger Receptor Class ◽  
Glycation End Products

Previous studies with peritoneal macrophages obtained from macrophage scavenger receptor class A (MSR-A) knock-out mice showed that the endocytic uptake of advanced glycation end products (AGE) by macrophages was mediated mainly by MSR-A. However, it is controversial whether the endocytic uptake of intravenously injected AGE proteins by liver sinusoidal endothelial cells (LECs) is similarly explained by receptor-mediated endocytosis via MSR-A. The present study was conducted to compare the capacity to endocytose AGE proteins in LECs and peritoneal macrophages obtained from MSR-A knock-out and littermate wild-type mice. The endocytic degradation capacity of MSR-A knock-out LECs for AGE–BSA was indistinguishable from that of wild-type LECs, whereas that of MSR-A knock-out peritoneal macrophages for AGE–BSA was decreased to 30% of that in wild-type cells. Similarly, the endocytic degradation of MSR-A knock-out LECs for acetylated low-density lipoprotein (acetyl-LDL) did not differ from that of wild-type LECs, whereas the endocytic degradation of acetyl-LDL by MSR-A knock-out peritoneal macrophages was less than 20% of that in wild-type cells. Furthermore, formaldehyde-treated serum albumin (f-Alb), a ligand known to undergo scavenger-receptor-mediated endocytosis by LECs, was effectively taken up by MSR-A knock-out LECs at a capacity that did not differ from that of wild-type LECs. Moreover, the endocytic uptake of AGE–BSA by LECs was effectively competed for by unlabelled f-Alb or acetyl-LDL. These results indicate that the scavenger-receptor ligands AGE proteins, acetyl-LDL and f-Alb are endocytosed by LECs through a non-MSR-A pathway.

scholarly journals Uptake and catabolism of modified LDL in scavenger-receptor class A type I/II knock-out mice

1998 ◽  
Vol 331 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Theo J. C. VAN BERKEL ◽  
Agnes VAN VELZEN ◽  
Johan K. KRUIJT ◽  
Hiroshi SUZUKI ◽  
Tatsushiko KODAMA
Keyword(s):  
Kupffer Cells ◽  
Scavenger Receptor ◽  
Peritoneal Macrophages ◽  
Scavenger Receptors ◽  
Liver Uptake ◽  
Knock Out ◽  
Class A ◽  
Scavenger Receptor Class ◽  
Knock Out Mice

The liver is the major organ responsible for the uptake of modified low-density lipoprotein (LDL) from the blood circulation, with endothelial and Kupffer cells as major cellular uptake sites. Scavenger-receptors, which include various classes, are held responsible for this uptake. Mice deficient in scavenger-receptor class A types I and II were created and the fate of acetylated LDL (Ac-LDL) in vivo and its interaction with liver endothelial, Kupffer and peritoneal macrophages was characterized. Surprisingly, the decay in vivo (t½ < 2 min), tissue distribution and liver uptake (at 5 min it was 77.4±4.6% of the injected dose) of Ac-LDL in the knock-out mice were not significantly different from control mice (t½ < 2 min and liver uptake 79.1±4.6% of the injected dose). A separation of mice liver cells into parenchymal, endothelial and Kupffer cells 10 min after injection of Ac-LDL indicated that in both control and knock-out mice the liver endothelial cells were responsible for more than 70% of the liver uptake. Both in control and knock-out mice, preinjection of polyinosinic acid (poly I, 200 µg) completely blocked the liver uptake, indicating that both in control and knock-out mice the scavenger-receptors are sensitive to poly I. Preinjection of suboptimal poly I concentrations (20 and 50 µg) provided evidence that the serum decay and liver uptake of Ac-LDL is more readily inhibited in the knock-out mice as compared with the control mice, indicating less efficient removal of Ac-LDL in vivo in the knock-out mice under these conditions. Studies in vitro with isolated liver endothelial and Kupffer cells from knock-out mice indicate that the cell association of Ac-LDL during 2 h at 37 °C is 50 and 53% of the control, respectively, whereas the degradation reaches values of 58 and 63%. For peritoneal macrophages from knock-out mice the cell association of Ac-LDL was identical to the control mice whereas the Ac-LDL degradation in cells from the knock-out mice was 17% of the control. The low degradation capacity of peritoneal macrophages from knock-out mice for Ac-LDL indicates that scavenger-receptor class A types I and II play a quantitative important role in the degradation of Ac-LDL by macrophages. In liver, the contribution of scavenger-receptor class A types I and II to the maximal uptake and degradation of Ac-LDL by endothelial and Kupffer cells was 40–50%. Binding studies performed at 4 °C indicate that the lower rates of degradation are due to a lower number of surface receptors on the cells from the knock-out mice. From the in vitro and in vivo data it can be concluded that in addition to the classic scavenger-receptors class A types I and II liver does contain additional novel poly I-sensitive scavenger-receptors that facilitate efficient removal of Ac-LDL from the blood circulation. The availability of the scavenger-receptor class A types I and II knock-out mice will stimulate further molecular identification of these receptors.

scholarly journals The Effect of Class A Scavenger Receptor Deficiency in Bone

2006 ◽  
Vol 282 (7) ◽  
pp. 4653-4660 ◽  
Author(s):  
Yi-Ling Lin ◽  
Willem J. S. de Villiers ◽  
Beth Garvy ◽  
Steven R. Post ◽  
Tim R. Nagy ◽  
...  
Keyword(s):  
Body Mass ◽  
Fat Body ◽  
Osteoclast Differentiation ◽  
Scavenger Receptor ◽  
Wild Type ◽  
Mineral Density ◽  
Knock Out ◽  
Class A ◽  
Significant Difference ◽  
Class A Scavenger Receptor

Class A scavenger receptor (SR-A) is predominantly expressed by macrophages, and because osteoclasts are of monocyte/macrophage lineage, SR-A is of potential interest in osteoclast biology. In addition to modified low density lipoprotein uptake, SR-A is also important in cell attachment and signaling. In this study we evaluated the effect of SR-A deletion on bone. Knock-out animals have 40% greater body weight than wild type. Body composition analyses demonstrated that total lean and fat body mass were greater in knock-out animals, but there was no significant difference in percent fat and lean body mass. Bone mineral density and content were significantly greater in knock-out compared with wild type animals. Micro-computed tomography analyses confirmed that total volume, bone volume as well as trabecular number, thickness, and connectivity were significantly greater in knock-out mice. As expected, trabecular separation was greater in wild type mice. The phenotype appears to be explained by 60% fewer osteoclasts in females and 35% fewer in males compared to wild type mice with a paradoxical increase in nuclei/osteoclast in knock-out animals. Furthermore, there were no differences in adipocyte number and osteoblast number or activity. The addition of the soluble extracellular domain of SR-A to RAW264.7 cells stimulated a concentration-dependent increase in osteoclast differentiation that was receptor activator of nuclear factor-κB ligand (RANKL)-dependent. Soluble SR-A had no effect on cell proliferation in the presence of RANKL but stimulated a 40% increase in numbers in the absence of RANKL. We conclude that SR-A plays a role in normal osteoclast differentiation, suggesting a novel role for this receptor in bone biology.

scholarly journals A comparative study of sulphated polysaccharide effects on advanced glycation end-product uptake and scavenger receptor class A level in macrophages

2020 ◽  
Vol 17 (1) ◽  
pp. 147916411989697 ◽  
Author(s):  
Takashi Nishinaka ◽  
Shuji Mori ◽  
Yui Yamazaki ◽  
Atsuko Niwa ◽  
Hidenori Wake ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Chondroitin Sulphate ◽  
Scavenger Receptor ◽  
Dextran Sulphate ◽  
Advanced Glycation ◽  
Sulphated Polysaccharides ◽  
Advanced Glycation End Product ◽  
Class A ◽  
Glycation End Products ◽  
End Products

Advanced glycation end-products, especially toxic advanced glycation end-products derived from glyceraldehyde (advanced glycation end-product-2) and glycolaldehyde (advanced glycation end-product-3), are biologically reactive compounds associated with diabetic complications. We previously demonstrated that toxic advanced glycation end-products were internalised into macrophage-like RAW264.7 cells through scavenger receptor-1 class A (CD204). Toxic advanced glycation end-product uptake was inhibited by fucoidan, a sulphated polysaccharide and antagonistic ligand for scavenger receptors, suggesting that sulphated polysaccharides are emerging candidates for treatment of advanced glycation end-product–related diseases. In this study, we compared the effects of six types of sulphated and non-sulphated polysaccharides on toxic advanced glycation end-product uptake in RAW264.7 cells. Fucoidan, carrageenan and dextran sulphate attenuated toxic advanced glycation end-product uptake. Fucoidan and carrageenan inhibited advanced glycation end-product-2–induced upregulation of SR-A, while advanced glycation end-product-3–induced upregulation of scavenger receptor-1 class A was only suppressed by fucoidan. Dextran sulphate did not affect scavenger receptor-1 class A levels in toxic advanced glycation end-product–treated cells. Chondroitin sulphate, heparin and hyaluronic acid failed to attenuate toxic advanced glycation end-product uptake. Heparin and hyaluronic acid had no effect on scavenger receptor-1 class A levels, while chondroitin sulphate inhibited advanced glycation end-product-3–induced upregulation of scavenger receptor-1 class A. Taken together, fucoidan and carrageenan, but not the other sulphated polysaccharides examined, had inhibitory activities on toxic advanced glycation end-product uptake and toxic advanced glycation end-product–induced upregulation of scavenger receptor-1 class A, possibly because of structural differences among sulphated polysaccharides.

Sign in / Sign up

Export Citation Format

Share Document