The HDL synapse: Decoding a complex interaction network of HDL residing proteins and endothelial cell surface receptors

2020 ◽  
Vol 315 ◽  
pp. e10
Author(s):  
K. Frey ◽  
S. Goetze ◽  
M. Mueller ◽  
L. Rohrer ◽  
A. Von Eckardstein ◽  
...  
2021 ◽  
Author(s):  
Jonas Goretzko ◽  
Nicole Heitzig ◽  
Katharina Thomas ◽  
Einar Kleinhans Krogsaeter ◽  
Johannes Nass ◽  
...  

In response to pro-inflammatory challenges including pathogenic attack and tissue damage, the endothelial cell surface is rearranged to present leukocyte-engaging cell surface receptors. The initial contact needed for leukocyte tethering and rolling is mediated via adhesion demand-driven exocytosis of Weibel-Palade bodies (WPB) that contain the leukocyte receptor P-selectin together with the stabilizing co-factor CD63. We found that diminished expression of the endolysosomal non-selective cation channel TPC2 or inhibition of TPC2-mediated Ca2+-release via trans-Ned 19 led to reduced endolysosomal Ca2+ efflux, and blocked transfer of CD63 from late endosomes/lysosomes (LEL) to WPB, and a concomitant loss of P-selectin on the endothelial cell surface. Accordingly, P-selectin-mediated leukocyte recruitment to trans-Ned 19-treated HUVEC under flow was significantly reduced without disturbing VWF exocytosis. Our findings establish the endolysosome-related TPC2 Ca2+ channel as a key element in the maintenance of proper endothelial functions and a potential pharmacological target in the control of inflammatory leukocyte recruitment.


1998 ◽  
Vol 334 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Nicholas S. BROWN ◽  
Roy BICKNELL

Angiogenesis is the term used to describe the formation of new blood vessels from the existing vasculature. In order to attract new vessels, a tissue must release an endothelial-cell chemoattractant. 2-Deoxy-d-ribose is produced in vivo by the catalytic action of thymidine phosphorylase (TP) on thymidine and has recently been identified as an endothelial-cell chemoattractant and angiogenesis-inducing factor. TP, previously known only for its role in nucleotide salvage, is now known to be angiogenic. TP expression is elevated in many solid tumours and in chronically inflamed tissues, both known areas of active angiogenesis. There is evidence that TP is also involved in physiological angiogenesis such as endometrial angiogenesis during the menstrual cycle. The majority of known endothelial-cell chemoattractants are polypeptides that bind to endothelial-cell-surface receptors. In contrast, 2-deoxy-d-ribose appears to lack a cell-surface receptor. Glucose is another sugar that acts as an endothelial-cell chemoattractant. The migratory activity of glucose is blocked by ouabain. It is possible that 2-deoxy-d-ribose and glucose stimulate endothelial-cell migration via a similar mechanistic pathway.


Small ◽  
2015 ◽  
Vol 11 (8) ◽  
pp. 1012-1012
Author(s):  
Ramesh Ramji ◽  
Cheong Fook Cheong ◽  
Hiroaki Hirata ◽  
Abdur Rub Abdur Rahman ◽  
Chwee Teck Lim

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