scholarly journals Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation

2005 ◽  
Vol 201 (7) ◽  
pp. 1113-1123 ◽  
Author(s):  
Rubina W. Saeed ◽  
Santosh Varma ◽  
Tina Peng-Nemeroff ◽  
Barbara Sherry ◽  
David Balakhaneh ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Leukocyte Recruitment ◽  
Dependent Manner ◽  
Cholinergic Stimulation ◽  
Endothelial Cell Activation ◽  
Cholinergic Agonists ◽  
Α7 Nachr

Endothelial cell activation plays a critical role in regulating leukocyte recruitment during inflammation and infection. Based on recent studies showing that acetylcholine and other cholinergic mediators suppress the production of proinflammatory cytokines via the α7 nicotinic acetylcholine receptor (α7 nAChR) expressed by macrophages and our observations that human microvascular endothelial cells express the α7 nAChR, we examined the effect of cholinergic stimulation on endothelial cell activation in vitro and in vivo. Using the Shwartzman reaction, we observed that nicotine (2 mg/kg) and the novel cholinergic agent CAP55 (12 mg/kg) inhibit endothelial cell adhesion molecule expression. Using endothelial cell cultures, we observed the direct inhibitory effects of acetylcholine and cholinergic agents on tumor necrosis factor (TNF)-induced endothelial cell activation. Mecamylamine, an nAChR antagonist, reversed the inhibition of endothelial cell activation by both cholinergic agonists, confirming the antiinflammatory role of the nAChR cholinergic pathway. In vitro mechanistic studies revealed that nicotine blocked TNF-induced nuclear factor–κB nuclear entry in an inhibitor κB (IκB)α- and IκBε-dependent manner. Finally, with the carrageenan air pouch model, both vagus nerve stimulation and cholinergic agonists significantly blocked leukocyte migration in vivo. These findings identify the endothelium, a key regulator of leukocyte trafficking during inflammation, as a target of anti-inflammatory cholinergic mediators.

Biocompatibility and Inflammation Profile of B2A-Coated Granules Used in Arthrodesis

2013 ◽  
Vol 32 (2) ◽  
pp. 154-161 ◽  
Author(s):  
Paul O. Zamora ◽  
Yi Liu ◽  
Henry Guo ◽  
Xinhua Lin
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Skin Irritation ◽  
Leukocyte Recruitment ◽  
Delayed Type Hypersensitivity ◽  
Endothelial Cell Activation ◽  
Air Pouch ◽  
Coated Granules

The biocompatibility/inflammation profile of B2A-coated ceramic granules was evaluated using a panel of standard biocompatibility protocols (International Organization for Standardization-10993) including skin irritation and delayed-type hypersensitivity (Kligman maximization test), as well as acute, subacute, and chronic toxicity. Additionally, the potential of B2A-coated granules to elicit inflammatory reactions was also assessed using in vivo air pouch models, and B2A was evaluated using in vitro models of leukocyte recruitment and endothelial cell activation. Overall, the findings demonstrate that B2A-coated ceramic granules exhibit good biocompatibility profiles in the murine air pouch model and in standard subcutaneous implant models, and B2A did not demonstrate evidence of leukocyte recruitment or endothelial cell activation. These findings suggest that B2A and B2A-coated granules have little, if any, propensity to initiate inflammation reactions based on leukocyte recruitment. Thus, traditional biocompatibility and specially designed inflammation models indicate a high degree of biocompatibility and a low possibility of toxicity, inflammation, or edema following the implant of B2A-coated granules.

scholarly journals Ethanol Blocks Leukocyte Recruitment and Endothelial Cell Activation In Vivo and In Vitro

2004 ◽  
Vol 173 (10) ◽  
pp. 6376-6383 ◽  
Author(s):  
Rubina W. Saeed ◽  
Santosh Varma ◽  
Tina Peng ◽  
Kevin J. Tracey ◽  
Barbara Sherry ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Leukocyte Recruitment ◽  
Endothelial Cell Activation

432. How do antiphospholipid antibodies contribute to preeclampsia?

2008 ◽  
Vol 20 (9) ◽  
pp. 112
Author(s):  
Q. Chen ◽  
C. Viall ◽  
P. R. Stone ◽  
L. W. Chamley
Keyword(s):  
Endothelial Cell ◽  
Antiphospholipid Antibodies ◽  
Cell Activation ◽  
Fold Increase ◽  
First Trimester ◽  
Endothelial Activation ◽  
Maternal Blood ◽  
Endothelial Cell Activation

Preeclampsia is characterised by elevated maternal blood pressure which is preceded by endothelial activation. The cause of this endothelial cell dysfunction is unclear but it appears to be triggered by a placental factor. One of the risk factors for developing preeclampsia is the presence of antiphospholipid antibodies (aPL) in the maternal blood but exactly how aPL predispose women to developing preeclampsia is unclear. A second feature known to be associated with preeclampsia is excessive shedding and deportation of dead trophoblasts. We have previously shown that shed trophoblasts are phagocytosed by endothelial cells and that phagocytosis of necrotic trophoblasts leads to endothelial cell activation1. In this study we examined the hypothesis that aPL alter the number or nature of trophoblasts shed from the placenta resulting in endothelial cell activation. Using our published model of trophoblast shedding 2 human first trimester placental explants were treated with monoclonal aPL, IIC5 or ID2, or control antibody CD45 for 72 h. Shed trophoblasts then were harvested and counted using a Cellometer AutoT4 automated cell counter. The activity of caspases 3&7 was analysed in all treated shed trophoblasts using a FLICA™ kit. The treated shed trophoblasts also were exposed to the endothelial cell line HMEC-1 for 24 h. The level of ICAM-1 by HMEC-1 was determined by cell-based ELISA. The number of trophoblasts shed from placental explants was increased 2 fold following aPL treatment whereas, treatment with CD45 resulted in only a 1.3 fold increase in shedding. Trophoblasts shed from aPL-treated explants contained less active caspases 3 & 7 compared with control shed trophoblasts. Moreover, phagocytosis of trophoblasts shed from aPL-treated explants induced significantly increased expression of ICAM-1 compared with controls. aPL treatment affected the number and nature of trophoblasts shed from placentae in such a way that phagocytosing endothelium become activated. These findings suggest that aPL treatment may have shifted the type of cell death that shed trophoblasts are undergoing from apoptosis to a more necrotic or aponecrotic mechanism. This type of shedding of trophoblasts in vivo might contribute to the endothelial cell activation which is a hallmark feature of preeclampsia. (1) Chen Q, Stone PR, McCowan LM et al. Phagocytosis of necrotic but not apoptotic trophoblasts induces endothelial cell activation. Hypertension. 2006;47:116–121. (2) Abumaree MH, Stone PR, Chamley LW. An in vitro model of human placental trophoblast deportation/shedding. Mol Hum Reprod. 2006;12:687–694.

scholarly journals Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals.

1995 ◽  
Vol 182 (6) ◽  
pp. 1857-1864 ◽  
Author(s):  
M J Yellin ◽  
J Brett ◽  
D Baum ◽  
A Matsushima ◽  
M Szabolcs ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Cd40 Expression

CD40 is expressed on a variety of cells, including B cells, monocytes, dendritic cells, and fibroblasts. CD40 interacts with CD40L, a 30-33-kD activation-induced CD4+ T cell surface molecule. CD40L-CD40 interactions are known to play key roles in B cell activation and differentiation in vitro and in vivo. We now report that normal human endothelial cells also express CD40 in situ, and CD40L-CD40 interactions induce endothelial cell activation in vitro. Frozen sections from normal spleen, thyroid, skin, muscle, kidney, lung, or umbilical cord were studied for CD40 expression by immunohistochemistry. Endothelial cells from all tissues studied express CD40 in situ. Moreover, human umbilical vein endothelial cells (HUVEC) express CD40 in vitro, and recombinant interferon gamma induces HUVEC CD40 upregulation. CD40 expression on HUVEC is functionally significant because CD40L+ Jurkat T cells or CD40L+ 293 kidney cell transfectants, but not control cells, upregulate HUVEC CD54 (intercellular adhesion molecule-1), CD62E (E-selectin), and CD106 (vascular cell adhesion molecule-1) expression in vitro. Moreover, the kinetics of CD40L-, interleukin 1-, or tumor necrosis factor alpha-induced CD54, CD62E, and CD106 upregulation on HUVEC are similar. Finally, CD40L-CD40 interactions do not induce CD80, CD86, or major histocompatibility complex class II expression on HUVEC in vitro. These results demonstrate that CD40L-CD40 interactions induce endothelial cell activation in vitro. Moreover, they suggest a mechanism by which activated CD4+ T cells may augment inflammatory responses in vivo by upregulating the expression of endothelial cell surface adhesion molecules.

Imaging fibrin formation and platelet and endothelial cell activation in vivo

2011 ◽  
Vol 105 (05) ◽  
pp. 776-782 ◽  
Author(s):  
Bruce Furie ◽  
Lola Bellido-Martin ◽  
Vivien Chen ◽  
Reema Jasuja ◽  
Barbara Furie
Keyword(s):  
Blood Flow ◽  
Endothelial Cell ◽  
Animal Models ◽  
Cell Activation ◽  
In Vitro Assays ◽  
Endothelial Cell Activation ◽  
The Past ◽  
Injury Model

SummaryOver the past six decades research employing in vitro assays has identified enzymes, cofactors, cell receptors and associated ligands important to the haemostatic process and its regulation. These studies have greatly advanced our understanding of the molecular and cellular bases of haemostasis and thrombosis. However, in vitro assays cannot simultaneously reproduce the interactions of all of the components of the haemostatic process that occur in vivo nor do they reflect the importance of haemodynamic factors resulting from blood flow. To overcome these limitations investigators have increasingly turned to animal models of haemostasis and thrombosis. In this article we describe some advances in the visualisation of platelet and endothelial cell activation and blood coagulation in vivo and review what we have learned from our intravital microscopy experiments using primarily the laser-induced injury model for thrombosis.

scholarly journals Integrin αVβ3as a Target for Blocking HIV-1 Tat-Induced Endothelial Cell Activation In Vitro and Angiogenesis In Vivo

2005 ◽  
Vol 25 (11) ◽  
pp. 2315-2320 ◽  
Author(s):  
Chiara Urbinati ◽  
Stefania Mitola ◽  
Elena Tanghetti ◽  
Chandra Kumar ◽  
Johannes Waltenberger ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Hiv 1

scholarly journals The In Vitro and In Vivo Effects of Anti-Galactose Antibodies on Endothelial Cell Activation and Xenograft Rejection

2003 ◽  
Vol 170 (3) ◽  
pp. 1531-1539 ◽  
Author(s):  
Hui Xu ◽  
Dengping Yin ◽  
Bashoo Naziruddin ◽  
Libing Chen ◽  
Aileen Stark ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Xenograft Rejection ◽  
In Vivo Effects

CHOLINERGIC ACTIVATION OF ENDOTHELIAL CELL ACTIVATION IN VITRO AND IN VIVO BY NICOTINE

Shock ◽  
2004 ◽  
Vol 21 ◽  
pp. 80
Author(s):  
C. N. Metz ◽  
R. Saeed ◽  
T. Penq ◽  
K. J. Tracey ◽  
S. Varma
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Cholinergic Activation

scholarly journals Dengue Virus Induces the Expression and Release of Endocan from Endothelial Cells by an NS1–TLR4-Dependent Mechanism

2021 ◽  
Vol 9 (6) ◽  
pp. 1305
Author(s):  
Carlos Alonso Domínguez-Alemán ◽  
Luis Alberto Sánchez-Vargas ◽  
Karina Guadalupe Hernández-Flores ◽  
Andrea Isabel Torres-Zugaide ◽  
Arturo Reyes-Sandoval ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cell Activation ◽  
Dengue Infection ◽  
Elevated Serum ◽  
Fold Increase ◽  
Endothelial Cell Activation ◽  
Stimulation Of

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.

Abstract MP27: Human Hypertension And Endothelial Cell Activation Promote The Formation And Activation Of Axl + Siglec-6 + Dendritic Cells Via Endothelial Release Of Growth Arrest Specific 6

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Justin P Van Beusecum ◽  
Natalia R Barbaro ◽  
Charles D Smart ◽  
David M Patrick ◽  
Cyndya A Shibao ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Endothelial Cells ◽  
Dendritic Cells ◽  
Endothelial Cell ◽  
Cell Activation ◽  
Growth Arrest ◽  
Positive Association ◽  
Endothelial Cell Activation ◽  
Human Hypertension

We have shown that dendritic cells (DCs) from hypertensive mice convey hypertension when adoptively transferred to recipients. Recently a novel subset of DCs in humans that express Axl and Sigelc-6 + (AS DCs) have been identified which drive T cell proliferation and produce IL-1β, IL-6 and IL-23, consistent with DCs we have observed in hypertension. We hypothesized that AS cells are increased in hypertension and contribute to immune activation in this disease. We quantified circulating AS DCs by flow cytometry in normotensive (n=23) and hypertensive (n=11) subjects and found a more than 2-fold increase in circulating AS DCs in hypertensive compared to normotensive subjects (297 ± 73 vs. 108 ± 26/ml; p =0.0304). To investigate the mechanism by which AS DCs are formed in hypertension, we co-cultured human aortic endothelial cells (HAECs) undergoing either normotensive (5%) or hypertensive (10%) cyclical stretch for 48 hours with CD14 + monocytes from normotensive donors. Co-culture of monocytes with HAECs exposed to 10% stretch significantly increased AS DCs and AS DC IL-1β production when compared to 5% stretch alone as assessed by flow cytometry (21 ± 5 vs. 131 ± 32 IL-1β + AS DCs). Moreover, inhibition of Axl signaling with R248, completely abolished the production of IL-1β in AS DCs (34 ± 8 IL-1β + AS DCs). In additional experiments we found that 10% stretch caused a 50% increase in release of growth arrest 6 (GAS6), the ligand for Axl, from HAECs compared to 5% stretch. Treatment of human monocytes with GAS6 mimicked the effect of 10% stretch in promoting AS cell formation and IL-1β production. Based on the increased secretion of GAS6 from HAECs, we used a J-wire to harvest human endothelial cells from 23 additional volunteers to assess endothelial cell activation and GAS6 secretion in vivo. We found a positive association between pulse pressure and plasma GAS6 (R 2 =0.25, p =0.0079) and a striking positive association between GAS6 and ICAM-1 (R 2 =0.39, p =0.0012). These data show that secretion of GAS6 by an activated endothelial seems to promote the formation and activation of AS DCs. Thus, the interplay between endothelial-derived GAS6 and AS DCs seem to be an important mechanism in human hypertension and might be a novel therapeutic target for this disease.

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