scholarly journals Transcellular migration of leukocytes is mediated by the endothelial lateral border recycling compartment

2009 ◽  
Vol 206 (12) ◽  
pp. 2795-2808 ◽  
Author(s):  
Zahra Mamdouh ◽  
Alexei Mikhailov ◽  
William A. Muller

Leukocyte migration across endothelial cell borders (paracellular) and through endothelial cells (transcellular) appear to be distinct processes. During paracellular migration, membrane from a parajunctional reticulum of interconnected vesicles, the endothelial lateral border recycling compartment (LBRC), moves to surround the leukocyte in a kinesin-mediated, microtubule-dependent manner. We show that transcellular migration likewise requires targeted trafficking of LBRC membrane. We show that in addition to platelet/endothelial cell adhesion molecule (PECAM; CD31), CD99 and junctional adhesion molecule A (JAM-A), but apparently not vascular endothelial cell–specific cadherin (cadherin 5, CD144), are components of the LBRC. During transcellular migration, LBRC membrane invests the transmigrating leukocyte. Intracellular adhesion molecule 1 (ICAM-1) on the apical endothelial surface is enriched around adherent leukocytes. Depolymerization of microtubules has no effect on ICAM-1 enrichment but blocks targeted trafficking of LBRC membrane and transcellular migration by >90%. Similar to their effects on paracellular transmigration, antibodies against PECAM or CD99, but not JAM-A, block transcellular migration. We conclude that similar molecular mechanisms promote both para- and transcellular migration.

2019 ◽  
Vol 16 (3) ◽  
pp. 175-184
Author(s):  
Sakaewan OUNJAIJEAN ◽  
Sukanya CHACHIYO ◽  
Kanokwan KULPRACHAKARN ◽  
Kongsak BOONYAPRANAI ◽  
Somdet SRICHAIRATANAKOOL ◽  
...  

Oxidative stress and inflammation are 2 major contributors to numerous life-threatening disorders, including vascular pathologies. Shallots (Allium ascalonicum) are a type of red onion which grows in Southeast Asia. Bulbs of this plant are used both as a food ingredient and in traditional medicine. This study attempted to investigate the possible ways that juice extracted from Thai shallot (A.ascalonicum cv. Chiangmai) bulbs could be used in the prevention of cardiovascular complications. The antioxidative and anti-inflammatory effects of shallot juice extract (SHE) on human vascular endothelial cells (EA.hy926) were investigated. Cell viability was evaluated by MTT assay, membrane lipid peroxidation by thiobarbituric acid reactive substances assay, intracellular reactive oxygen species (ROS) production by the fluorescent probe 6-carboxy-2'-7'-dichlorofluoresceine, and interleukin-6 (IL-6) released by ELISA. The shallot juice showed extremely low cytotoxicity against EA.hy926 cells, with IC50 of 41.9 and 27.3 mg/ml for 24 h- and 48 h-incubation, respectively. SHE reduced the iron-induced malondialdehyde production in a dose-dependent manner. The extract also demonstrated antioxidant activity as shown by a significant reduction of H2O2-induced ROS production at a low concentration (< 200 mg/ml). Furthermore, SHE significantly attenuated the level of IL-6 released during lipopolysaccharide stimulation (p < 0.05). It is of interest that the juice extracted from Thai shallot bulbs demonstrated both cellular antioxidant and anti-inflammatory properties in endothelial cell models, combined with a reduction in toxicity. Shallot extract could be considered as a nutraceutical for the prevention or management of vascular diseases as it is related to oxidative stress and inflammation.


1995 ◽  
Vol 74 (06) ◽  
pp. 1573-1577 ◽  
Author(s):  
David B Gubler ◽  
Chad R Ahlstrom ◽  
Lihua Liu ◽  
Jin-Feng Zhou ◽  
Charles J Parker ◽  
...  

SummaryVascular endothelium regulates multiple aspects of platelet function through secretion of a variety of substances, including von Willebrand factor, nitric oxide, and prostacyclin (PGI2). The objective of this study was to determine whether procoagulant albumin (P-AI), a modified form of albumin present in normal human plasma could modulate endothelial cell secretion of these substances. P-AI did not affect constitutive secretion of von Willebrand factor or nitric oxide, but did increase PGI2 secretion in a time- and concentration-dependent manner. Pretreatment of endothelial cells with aspirin, or use of suramin, a broad- specificity inhibitor, prevented the response to P-AI. Prostaglandin H synthase-2 contributed to the P-AI-induced PGI2 secretion. These results indicate that in addition to inducing tissue factor activity and reducing protein C activation and fibrinolysis, P-AI also modulates vascular endothelial cell PGI2 secretion, and potentially, platelet function.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Changyou Li ◽  
Siyuan Li ◽  
Changkai Jia ◽  
Lingling Yang ◽  
Zicheng Song ◽  
...  

Previous studies showed that several members of the S100A family are involved in neovascularization and tumor development. This study checked whether low concentrations of S100A8 or S100A9 has any effect on the behaviour of vascular endothelial cells. A human umbilical vascular endothelial cell (HUVEC) line was used to measure vascular endothelial cell bioactivity related to angiogenesis, such as cell proliferation, migration, and vessel formation. In the low concentration range up to 10 μg/mL, either each alone or in combination, S100A8 and S100A9 proteins promoted proliferation of HUVEC cells in a dose-dependent manner. The presence of both proteins in culture showed additive effects over each single protein. Both proteins enhanced HUVEC cells to migrate across the transwell membrane and to form tube-like structures on the Matrigel surface. When mixed in Matrigel and injected subcutaneously in Balb/c mice, both proteins increased vessel development in the gel plugs. Microarray assay of HUVEC cells treated with 10 μg/mL S100A8 revealed that ribosome pathway, pathogenicEscherichia coliinfection pathway, apoptosis, and stress response genes were modulated by S100A8 treatment. We propose that S100A8 and S100A9 proteins from either infiltrating inflammatory cells or tumor cells play an important role in the interplay among inflammation, angiogenesis, and tumorigenesis.


Toxins ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 102 ◽  
Author(s):  
Florence Chalier ◽  
Laura Mugnier ◽  
Marion Tarbe ◽  
Soioulata Aboudou ◽  
Claude Villard ◽  
...  

In the soft treatment of cancer tumours, consequent downregulation of the malignant tissue angiogenesis constitutes an efficient way to stifle tumour development and metastasis spreading. As angiogenesis requires integrin–promoting endothelial cell adhesion, migration, and vessel tube formation, integrins represent potential targets of new therapeutic anti–angiogenic agents. Our work is a contribution to the research of such therapeutic disintegrins in animal venoms. We report isolation of one peptide, named Dabmaurin–1, from the hemotoxic venom of snake Daboia mauritanica, and we evaluate its potential anti–tumour activity through in vitro inhibition of the human vascular endothelial cell HMECs functions involved in tumour angiogenesis. Dabmaurin–1 altered, in a dose–dependent manner, without any significant cytotoxicity, HMEC proliferation, adhesion, and their mesenchymal migration onto various extracellular matrix proteins, as well as formation of capillary–tube mimics on MatrigelTM. Via experiments involving HMEC or specific cancers cells integrins, we demonstrated that the above Dabmaurin–1 effects are possibly due to some anti–integrin properties. Dabmaurin–1 was demonstrated to recognize a broad panel of prooncogenic integrins (αvβ6, αvβ3 or αvβ5) and/or particularly involved in control of angiogenesis (α5β1, α6β4, αvβ3 or αvβ5). Furthermore, mass spectrometry and partial N–terminal sequencing of this peptide revealed, it is close to Lebein–1, a known anti–β1 disintegrin from Macrovipera lebetina venom. Therefore, our results show that if Dabmaurin–1 exhibits in vitro apparent anti–angiogenic effects at concentrations lower than 30 nM, it is likely because it acts as an anti–tumour disintegrin.


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