scholarly journals Low density lipoprotein and very low density lipoprotein are selectively bound by aggregated C-reactive protein.

1982 ◽  
Vol 156 (1) ◽  
pp. 230-242 ◽  
Author(s):  
F C de Beer ◽  
A K Soutar ◽  
M L Baltz ◽  
I M Trayner ◽  
A Feinstein ◽  
...  

C-reactive protein (CRP), the classical acute-phase protein, can bind phospholipids by virtue of its specific, calcium-dependent reactivity with phosphorylcholine residues. However, analysis of acute-phase serum by gel filtration and by density gradient ultracentrifugation showed that the CRP was in a free, uncomplexed form, despite the coexistent presence of the various classes of serum lipoproteins, all of which contain phospholipids. In contrast, when isolated CRP was aggregated by immobilization at a sufficient density on a solid phase and then exposed to normal human serum, it selectively bound low density lipoprotein (LDL) and traces of very low density lipoprotein. The reaction was calcium dependent and reversible by free phosphorylcholine but not by heparin. LDL isolated from normal plasma was also bound by aggregated CRP. CRP reacts in vitro with a wide variety of different ligands both of extrinsic and of autogenous origin, e.g., microbial products and damaged cell membranes, respectively. If CRP aggregated in vivo by complexing with these ligands than acquires the capacity to selectively bind LDL, the phenomenon may have significant implications for the function of CRP and for the metabolism, clearance, and deposition of LDL.

2004 ◽  
Vol 91 (03) ◽  
pp. 522-530 ◽  
Author(s):  
Michael Dennis ◽  
Colin Downey ◽  
Nicole Brufatto ◽  
Michael Nesheim ◽  
Ken Stevenson ◽  
...  

SummaryThe biphasic waveform that can predict for disseminated intravascular coagulation (DIC) is due to the formation of a calcium-dependent complex between C reactive protein (CRP) and very low density lipoprotein (VLDL). As thrombin generation is pivotal to DIC, this aspect has been specifically investigated and the VLDL component has been found to increase prothrombinase activity via both quantitative and qualitative changes. The specific prothrombinase activity of VLDL from patients manifesting the biphasic waveform was 2.5 times that of normal individuals or critically ill patients without the biphasic waveform. This activity was due to an increase in anionic phospholipid surfaces that could be inhibited with excess annexin V and which was dependent on structurally intact apolipoprotein B.The qualitative change appeared to be due to a deficiency of phosphatidylethanolamine inVLDL from patients with the biphasic waveform.The functional consequence of this enhanced prothrombinase activity was an increased procoagulant effect in plasma. Using a modified activated partial thromboplastin time assay, the mean normal clot time decreased significantly when VLDL from patients with biphasic waveforms was substituted.These results indicate that VLDL derived from patients with the biphasic waveform can enhance thrombin procoagulant activity. As the CRP-VLDL complex exists in vivo, it could have a pathogenic role in disseminating the process of intravascular coagulation.


1983 ◽  
Vol 65 (3) ◽  
pp. 30P-30P
Author(s):  
I.F. Rowe ◽  
A.K. Soutar ◽  
I. Trayner ◽  
M.L. Baltz ◽  
F.C. de Beer ◽  
...  

2020 ◽  
Vol 204 (10) ◽  
pp. 2712-2721
Author(s):  
Zhenxing Cheng ◽  
Simon T. Abrams ◽  
Julien Toh ◽  
Susan S. Wang ◽  
Colin Downey ◽  
...  

FEBS Letters ◽  
2006 ◽  
Vol 580 (22) ◽  
pp. 5155-5160 ◽  
Author(s):  
Miguel L. Rufail ◽  
Samuel C. Ramage ◽  
Rik van Antwerpen

2007 ◽  
Vol 7 (S1) ◽  
Author(s):  
Michael Nesheim ◽  
John Samis ◽  
John Walker ◽  
Timothy Fischer ◽  
Liliana Tejidor ◽  
...  

2002 ◽  
Vol 366 (1) ◽  
pp. 195-201 ◽  
Author(s):  
Tao FU ◽  
Jayme BORENSZTAJN

Foam cells found in atherosclerotic lesions are believed to derive from macrophages that take up aggregated low-density lipoprotein (LDL) particles bound to the extracellular matrix of arterial walls. C-reactive protein (CRP) is an acute-phase protein found in atherosclerotic lesions, which when immobilized on a solid phase, can bind and cluster LDL particles in a calcium-dependent manner. In the present study, we examined whether CRP-bound aggregated LDL could be taken up by macrophages in culture. CRP molecules were aggregated in the presence of calcium and immobilized on the surface of polystyrene microtitre wells. Human LDL added to the wells bound to and aggregated on the immobilized CRP, also in a calcium-dependent manner. On incubation with macrophages, the immobilized CRP-bound LDL aggregates were readily taken up by the cells, as demonstrated by immunofluorescence microscopy, by the cellular accumulation of cholesterol and by the overexpression of adipophilin. Immunofluorescence microscopy and flow-cytometry analysis established that the uptake of the LDL—CRP complex was not mediated by the CRP receptor CD32. These observations with immobilized CRP and LDL, approximating the conditions that exist in the extracellular matrix of the arterial wall, thus suggest that CRP may contribute to the formation of foam cells in atherosclerotic lesions by causing the aggregation of LDL molecules that are then taken up by macrophages through a CD32-independent pathway.


Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2522-2529 ◽  
Author(s):  
Cheng Hock Toh ◽  
John Samis ◽  
Colin Downey ◽  
John Walker ◽  
Lev Becker ◽  
...  

A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low–density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca++ to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The Kd of the CRP/VLDL interaction is 340 nM, and the IC50 for Ca++ is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 μg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP–VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.


2001 ◽  
Vol 1 (S2) ◽  
Author(s):  
Michael Nesheim ◽  
John Samis ◽  
John Walker ◽  
Timothy Fischer ◽  
Liliana Tejidor ◽  
...  

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