The Low Density Lipoprotein Receptor on Human Peripheral Blood Monocytes and Lymphocytes: Visualization by Ligand Blotting and Immunoblotting Techniques*

1986 ◽  
Vol 62 (6) ◽  
pp. 1279-1287 ◽  
Author(s):  
CLAY F. SEMENKOVICH ◽  
RICHARD E. OSTLUND
Keyword(s):  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Density Lipoprotein Receptor ◽  
Monocytes And Lymphocytes

scholarly journals Differential endocytosis of tissue plasminogen activator by serpins PAI-1 and PAI-2 on human peripheral blood monocytes

2010 ◽  
Vol 104 (12) ◽  
pp. 1133-1142 ◽  
Author(s):  
Jodi A. Lee ◽  
David R. Croucher ◽  
Marie Ranson
Keyword(s):  
Peripheral Blood ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Blood Monocytes ◽  
Low Density Lipoprotein Receptor ◽  
Peripheral Blood Monocytes ◽  
Density Lipoprotein Receptor ◽  
Pai 1

SummaryGeneration of the broad spectrum protease plasmin is facilitated by the tissue (t-PA) and urokinase (u-PA) plasminogen activators, within multiple physiological and disease states. Finely tuned control of this proteolytic cascade is exerted by the plasminogen activator inhibitors type-1 (PAI-1/SERPINE1) and 2 (PAI-2/SERPINB2). Expression of this network of activators and inhibitors by cells of myeloid lineage appears to be highly interchangeable between physiological environments, and whilst the role of PAI-1 and PAI-2 in regulating u-PA-dependent functions is well established, the interaction between t-PA and PAI-2 on these cell types is poorly characterised. To this end, we used freshly isolated peripheral blood monocytes (PBM) as a model of a t-PA-dependent cellular environment. We demonstrate that while both PAI-1 and PAI-2 could inhibit surface-bound t-PA and are internalised predominately via low-density-lipoprotein receptor family members, PAI-1 enhanced the endocytosis of t-PA, whereas PAI-2 did not. Surface plasmon resonance analyses revealed differential binding affinities between the very-low-density-lipoprotein receptor and t-PA and t-PA:PAI-1 complexes in addition to those previously described with low-density-lipoprotein receptor-related protein. Moreover, t-PA:PAI-2 bound to both endocytosis receptors with similar kinetics to t-PA. These differential biochemical interactions between t-PA and the t-PA:PAI complexes may underlie the observed differences in endocytosis mechanisms on the PBMs. This suggests that while PAI-1 and PAI-2 function similarly in the control of cellular plasmin generation by t-PA, they may have disparate effects on the alternative functions of t-PA via modulation of its engagement with endocytosis receptors.

Abstract 411: Obesity Alters the Expression of Very Low Density Lipoprotein Receptor (vldlr) Expression in Peripheral Blood Monocytes: Possible Links Between Vldlr Expression and Monocyte Phenotypes

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Tahar Hajri ◽  
Brian Johnson ◽  
George Mazpule ◽  
Toghrul Talishinskiy ◽  
Sebastian Eid ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Blood Monocytes ◽  
Low Density Lipoprotein Receptor ◽  
Peripheral Blood Monocytes ◽  
Density Lipoprotein Receptor ◽  
Obese Subjects

Objective: Very low density lipoprotein receptor (VLDLR) is a member of the low-density lipoprotein receptor family that binds multiple ligands including TG-rich lipoproteins. The role of VLDLR in lipid uptake had been demonstrated in cell culture and animal models, but little is known about the effects of obesity on VLDLR expression in human. Accordingly, we examined the impact of obesity on VLDLR expression in peripheral blood monocytes and explored possible links with monocyte inflammatory markers and circulating lipids. Subjects and measurements: Blood was collected from a total of 69 subjects including 23 normal-weight (body mass index: BMI < 25 kg/m 2 ) controls and 46 obese (BMI > 30 kg/m 2 ) subjects. Blood lipids, glucose and hormones were measured. Monocytes were isolated from buffy coats using Ficoll density centrifugation followed by magnetic separation of CD14-positive cells with magnetic beads. Expression of VLDLR, and pro- and ant-inflammatory markers of monocytes was examined by western blotting and quantitative qPCR. The uptake of labeled VLDL (DiI-VLDL) was also assessed in monocyte cultures. Results: Insulin, and total and VLDL triglycerides were increased in plasma of obese subjects. In addition, VLDLR protein and mRNA levels were significantly (p< 0.05) higher (~ 40%) in obese compared to lean subjects. Monocytes of obese subjects exhibited higher expression of IL-6 and TNF-α (+29 to 43%), but lower expression of IL-10 and CD163 (-30 to 47%). The levels of monocyte VLDLR was positively correlated with blood triglycerides and insulin, and negatively with adiponectin. The uptake of labeled VLDL, assessed by fluorescence microscope, was higher in monocytes of obese subjects. Conclusions: Our findings indicate that obesity upregulates the expression of VLDLR and pro-inflammatory markers in peripheral blood monocytes. The uptake VLDL was also increased in monocyte of obese subjects suggesting that obesity-induced VLDLR expression may explain the changes of VLDL uptake and monocyte phenotype.

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