scholarly journals Effects of Microvesicles Derived from NK Cells Stimulated with IL-1β on the Phenotype and Functional Activity of Endothelial Cells

2021 ◽  
Vol 22 (24) ◽  
pp. 13663
Author(s):  
Kseniia Markova ◽  
Valentina Mikhailova ◽  
Yulia Milyutina ◽  
Andrey Korenevsky ◽  
Anastasia Sirotskaya ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Nk Cells ◽  
Cell Line ◽  
Functional Activity ◽  
Caspase 3 ◽  
Migratory Activity ◽  
Cell Functions ◽  
Endothelial Cell Death

Microvesicles (MVs) are plasma extracellular vesicles ranging from 100 (150) to 1000 nm in diameter. These are generally produced by different cells through their vital activity and are a source of various protein and non-protein molecules. It is assumed that MVs can mediate intercellular communication and modulate cell functions. The interaction between natural killer cells (NK cells) and endothelial cells underlies multiple pathological conditions. The ability of MVs derived from NK cells to influence the functional state of endothelial cells in inflammatory conditions has yet to be studied well. In this regard, we aimed to study the effects of MVs derived from NK cells of the NK-92 cell line stimulated with IL-1β on the phenotype, caspase activity, proliferation and migration of endothelial cells of the EA.hy926 cell line. Endothelial cells were cultured with MVs derived from cells of the NK-92 cell line after their stimulation with IL-1β. Using flow cytometry, we evaluated changes in the expression of endothelial cell surface molecules and endothelial cell death. We evaluated the effect of MVs derived from stimulated NK cells on the proliferative and migratory activity of endothelial cells, as well as the activation of caspase-3 and caspase-9 therein. It was established that the incubation of endothelial cells with MVs derived from cells of the NK-92 cell line stimulated with IL-1β and with MVs derived from unstimulated NK cells, leads to the decrease in the proliferative activity of endothelial cells, appearance of the pan leukocyte marker CD45 on them, caspase-3 activation and partial endothelial cell death, and reduced CD105 expression. However, compared with MVs derived from unstimulated NK cells, a more pronounced effect of MVs derived from cells of the NK-92 cell line stimulated with IL-1β was found in relation to the decrease in the endothelial cell migratory activity and the intensity of the CD54 molecule expression on them. The functional activity of MVs is therefore mediated by the conditions they are produced under, as well as their internal contents.

scholarly journals Induction of Caspase-Mediated Cell Death by Matrix Metalloproteinases in Cerebral Endothelial Cells after Hypoxia—Reoxygenation

2004 ◽  
Vol 24 (7) ◽  
pp. 720-727 ◽  
Author(s):  
Sun-Ryung Lee ◽  
Eng H. Lo
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Matrix Metalloproteinases ◽  
Caspase 3 ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Endothelial Cell Death ◽  
Cell Matrix Interactions ◽  
Hypoxia Reoxygenation

Matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral ischemia by degrading matrix components in the neurovascular unit. In this study, the authors document a pathway by which MMPs interfere with cell—matrix interactions and trigger caspase-mediated cytotoxicity in brain endothelial cells. Hypoxia—reoxygenation induced endothelial cytotoxicity. Cytoprotection with zDEVD-fmk confirmed that cell death was partly caspase mediated. The temporal profile of caspase-3 activation was matched by elevations in MMP-2 and MMP-9. MMP inhibitors significantly decreased caspase-3 activation and reduced endothelial cell death. Degradation of matrix fibronectin confirmed the presence of extracellular proteolysis. Increasing integrin-linked kinase signaling with the β1 integrin-activating antibody (8A2) ameliorated endothelial cytotoxicity. The results suggest that MMP-9 and MMP-2 contribute to caspase-mediated brain endothelial cell death after hypoxia—reoxygenation by disrupting cell—matrix interactions and homeostatic integrin signaling.

scholarly journals Temporal relationship between proliferating and apoptotic hormone-producing and endothelial cells in the equine corpus luteum

Reproduction ◽  
2006 ◽  
Vol 132 (1) ◽  
pp. 111-118 ◽  
Author(s):  
J Aguilar ◽  
H M Fraser ◽  
H Wilson ◽  
E Clutton ◽  
D J Shaw ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Luteal Phase ◽  
Temporal Relationship ◽  
Caspase 3 ◽  
Corpora Lutea ◽  
Histone 3 ◽  
Endothelial Cell Death

The temporal relationship between endothelial cell death, vascular regression and the death of hormone-producing cells in the mare has not been established. To determine the dynamics of cell proliferation and death throughout the luteal phase, corpora lutea were studied at the early, mid- and late luteal phase, and after treatment with cloprostenol in the mid-luteal phase to induce premature luteolysis. Changes in cell proliferation and apoptosis were investigated utilising specific markers (phosphorylated histone-3 and activated caspase-3 respectively). Histone-3 positive cells were most abundant during the early luteal phase, and were mainly present in endothelial cells. Histone-3 activity significantly increased in hormone-producing cells 36 h after cloprostenol treatment. Frequency of activated caspase-3 staining peaked on day 14, and was induced by 36 h after cloprostenol administration in mid-luteal phase. However, cell death occurred simultaneously in the endothelial and hormone-producing cells. These results show that a subset of hormone-producing cells enter the early stages of cell division around luteolysis, while the majority of cells are undergoing cell death. Natural and induced functional and structural luteal regression in the mare can be at least partially attributed to simultaneous apoptosis of endothelial and hormone-producing cells. However, there is no evidence that endothelial cell death is the trigger for naturally occurring luteolysis.

scholarly journals Role of thromboxane in retinal microvascular degeneration in oxygen-induced retinopathy

2001 ◽  
Vol 90 (6) ◽  
pp. 2279-2288 ◽  
Author(s):  
Martin H. Beauchamp ◽  
Ana Katherine Martinez-Bermudez ◽  
Fernand Gobeil ◽  
Anne Marilise Marrache ◽  
Xin Hou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Oxidant Stress ◽  
Microvascular Endothelial Cell ◽  
Oxygen Induced Retinopathy ◽  
Rat Pups ◽  
Endothelial Cell Death ◽  
Peroxidation Product ◽  
Synthase Inhibitor

Microvascular degeneration is an important event in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity. Because oxidant stress abundantly generates thromboxane A2(TxA2), we tested whether TxA2plays a role in retinal vasoobliteration of OIR and contributes to such vascular degeneration by direct endothelial cytotoxicity. Hyperoxia-induced retinal vasoobliteration in rat pups (80% O2exposure from postnatal days 5–14) was associated with increased TxB2generation and was significantly prevented by TxA2synthase inhibitor CGS-12970 (10 mg · kg−1· day−1) or TxA2-receptor antagonist CGS-22652 (10 mg · kg−1· day−1). TxA2mimetics U-46619 (EC5050 nM) and I-BOP (EC505 nM) caused a time- and concentration-dependent cell death of neuroretinovascular endothelial cells from rats as well as newborn pigs but not of smooth muscle and astroglial cells; other prostanoids did not cause cell death. The peroxidation product 8-iso-PGF2, which is generated in OIR, stimulated TxA2formation by endothelial cells and triggered cell death; these effects were markedly diminished by CGS-12970. TxA2-dependent neuroretinovascular endothelial cell death was mostly by necrosis and to a lesser extent by apoptosis. The data identify an important role for TxA2in vasoobliteration of OIR and unveil a so far unknown function for TxA2in directly triggering neuroretinal microvascular endothelial cell death. These effects of TxA2might participate in other ischemic neurovascular injuries.

Lysophosphatidic acid induces endothelial cell death by modulating the redox environment

2007 ◽  
Vol 292 (3) ◽  
pp. R1174-R1183 ◽  
Author(s):  
Sonia Brault ◽  
Fernand Gobeil ◽  
Audrey Fortier ◽  
Jean-Claude Honoré ◽  
Jean-Sébastien Joyal ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
P38 Mapk ◽  
Lysophosphatidic Acid ◽  
Umbilical Vein ◽  
Oxidant Stress ◽  
Redox Environment ◽  
Endothelial Cell Death

Oxidant stress plays a significant role in hypoxic-ischemic injury to the susceptible microvascular endothelial cells. During oxidant stress, lysophosphatidic acid (LPA) concentrations increase. We explored whether LPA caused cytotoxicity to neuromicrovascular cells and the potential mechanisms thereof. LPA caused a dose-dependent death of porcine cerebral microvascular as well as human umbilical vein endothelial cells; cell death appeared oncotic rather than apoptotic. LPA-induced cell death was mediated via LPA1 receptor, because the specific LPA1 receptor antagonist THG1603 fully abrogated LPA's effects. LPA decreased intracellular GSH levels and induced a p38 MAPK/JNK-dependent inducible nitric oxide synthase (NOS) expression. Pretreatment with the antioxidant GSH precursor N-acetyl-cysteine (NAC), as well as with inhibitors of NOS [ Nω-nitro-l-arginine (l-NNA); 1400W], significantly prevented LPA-induced endothelial cell death (in vitro) to comparable extents; as expected, p38 MAPK (SB203580) and JNK (SP-600125) inhibitors also diminished cell death. LPA did not increase indexes of oxidation (isoprostanes, hydroperoxides, and protein nitration) but did augment protein nitrosylation. Endothelial cytotoxicity by LPA in vitro was reproduced ex vivo in brain and in vivo in retina; THG1603, NAC, l-NNA, and combined SB-203580 and SP600125 prevented the microvascular rarefaction. Data implicate novel properties for LPA as a modulator of the cell redox environment, which partakes in endothelial cell death and ensued neuromicrovascular rarefaction.

scholarly journals Acanthamoeba castellanii Induces Host Cell Death via a Phosphatidylinositol 3-Kinase-Dependent Mechanism

2005 ◽  
Vol 73 (5) ◽  
pp. 2704-2708 ◽  
Author(s):  
James Sissons ◽  
Kwang Sik Kim ◽  
Monique Stins ◽  
Samantha Jayasekera ◽  
Selwa Alsam ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Acanthamoeba Castellanii ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Endothelial Cell Death ◽  
Microvascular Endothelial ◽  
Phosphatidylinositol 3

ABSTRACT Granulomatous amoebic encephalitis due to Acanthamoeba castellanii is a serious human infection with fatal consequences, but it is not clear how the circulating amoebae interact with the blood-brain barrier and transmigrate into the central nervous system. We studied the effects of an Acanthamoeba encephalitis isolate belonging to the T1 genotype on human brain microvascular endothelial cells, which constitute the blood-brain barrier. Using an apoptosis-specific enzyme-linked immunosorbent assay, we showed that Acanthamoeba induces programmed cell death in brain microvascular endothelial cells. Next, we observed that Acanthamoeba specifically activates phosphatidylinositol 3-kinase. Acanthamoeba-mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. These results were further confirmed using brain microvascular endothelial cells expressing dominant negative forms of phosphatidylinositol 3-kinase. This is the first demonstration that Acanthamoeba-mediated brain microvascular endothelial cell death is dependent on phosphatidylinositol 3-kinase.

scholarly journals Trauma-hemorrhagic shock-induced pulmonary epithelial and endothelial cell injury utilizes different programmed cell death signaling pathways

2009 ◽  
Vol 296 (3) ◽  
pp. L404-L417 ◽  
Author(s):  
Dimtrios Barlos ◽  
Edwin A. Deitch ◽  
Anthony C. Watkins ◽  
Frank J. Caputo ◽  
Qi Lu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Epithelial Cell ◽  
Programmed Cell Death ◽  
Lung Injury ◽  
Caspase 3 ◽  
Nuclear Translocation ◽  
A549 Cells ◽  
Mesenteric Lymph

Intestinal ischemia after trauma-hemorrhagic shock (T/HS) results in gut barrier dysfunction and the production/release of biologically active and tissue injurious factors in the mesenteric lymph, which, in turn, causes acute lung injury and a systemic inflammatory state. Since T/HS-induced lung injury is associated with pulmonary endothelial and epithelial cell programmed cell death (PCD) and was abrogated by mesenteric lymph duct ligation, we sought to investigate the cellular pathways involved. Compared with trauma-sham shock (T/SS) rats, a significant increase in caspase-3 and M30 expression was detected in the pulmonary epithelial cells undergoing PCD, whereas apoptosis-inducing factor (AIF), but not caspase-3, was detected in endothelial cells undergoing PCD. This AIF-mediated pulmonary endothelial PCD response was validated in an in situ femoral vein assay where endothelial cells were found to express AIF but not caspase-3. To complement these studies, human umbilical vein endothelial cell (HUVEC), human lung microvascular endothelial cell (HLMEC), and human alveolar type II epithelial cell (A549) lines were used as in vitro models. T/HS lymph induced the nuclear translocation of AIF in HUVEC and HLMEC, and caspase inhibition in these cells did not afford any cytoprotection. For proof of principle, AIF silencing in HUVEC reversed the cytotoxic effects of T/HS on cell viability and DNA fragmentation. In A549 cells, T/HS lymph activated caspase-3-mediated apoptosis, which was partially abrogated by N-benzyloxycarbonyl-Val-Ala-Asp (zVAD). Additionally, T/HS lymph did not cause the nuclear translocation of AIF in A549 cells. Collectively, T/HS-induced pulmonary endothelial PCD occurs via an AIF-dependent caspase-independent pathway, whereas epithelial cells undergo apoptosis by a caspase-dependent pathway.

scholarly journals Activation of Intrinsic and Extrinsic Proapoptotic Signaling Pathways in Interleukin-18-mediated Human Cardiac Endothelial Cell Death

2004 ◽  
Vol 279 (19) ◽  
pp. 20221-20233 ◽  
Author(s):  
Bysani Chandrasekar ◽  
Kirankumar Vemula ◽  
Rama Mohan Surabhi ◽  
Min Li-Weber ◽  
Laurie B. Owen-Schaub ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Signaling Pathways ◽  
Cell Apoptosis ◽  
Dominant Negative ◽  
Interleukin 18 ◽  
Endothelial Cell Apoptosis ◽  
Endothelial Cell Death ◽  
Fas L

Endothelial cells are the primary targets of circulating immune and inflammatory mediators. We hypothesize that interleukin-18, a proinflammatory cytokine, induces endothelial cell apoptosis. Human cardiac microvascular endothelial cells (HCMEC) were treated with interleukin (IL) 18. mRNA expression was analyzed by ribonuclease protection assay, protein levels by immunoblotting, and cell death by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter analysis. We also investigated the signal transduction pathways involved in IL-18-mediated cell death. Treatment of HCMEC with IL-18 increases 1) NF-κB DNA binding activity; 2) induces κB-driven luciferase activity; 3) induces IL-1β and TNF-α expression via NF-κB activation; 4) inhibits antiapoptotic Bcl-2 and Bcl-XL; 5) up-regulates proapoptotic Fas, Fas-L, and Bcl-XSexpression; 6) inducesfasand Fas-L promoter activities via NF-κB activation; 7) activates caspases-8, -3, -9, and BID; 8) induces cytochromecrelease into the cytoplasm; 9) inhibits FLIP; and 10) induces HCME cell death by apoptosis as seen by increased annexin V staining and increased levels of mono- and oligonucleosomal fragmented DNA. Whereas overexpression of Bcl-2 significantly attenuated IL-18-induced endothelial cell apoptosis, Bcl-2/Bcl-XLchimeric phosphorothioated 2′-MOE-modified antisense oligonucleotides potentiated the proapoptotic effects of IL-18. Furthermore, caspase-8, IKK-α, and NF-κB p65 knockdown or dominant negative IκB-α and dominant negative IκB-β or kinase dead IKK-β significantly attenuated IL-18-induced HCME cell death. Effects of IL-18 on cell death are direct and are not mediated by intermediaries such as IL-1β, tumor necrosis factor-α, or interferon-γ. Taken together, our results indicate that IL-18 activates both intrinsic and extrinsic proapoptotic signaling pathways, induces endothelial cell death, and thereby may play a role in myocardial inflammation and injury.

scholarly journals Semaphorin 6A regulates angiogenesis by modulating VEGF signaling

Blood ◽  
2012 ◽  
Vol 120 (19) ◽  
pp. 4104-4115 ◽  
Author(s):  
Marta Segarra ◽  
Hidetaka Ohnuki ◽  
Dragan Maric ◽  
Ombretta Salvucci ◽  
Xu Hou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Retinal Vessels ◽  
Vegf Signaling ◽  
Endothelial Cell Survival ◽  
Complex Process ◽  
Mouse Tissues ◽  
Endothelial Cell Death ◽  
Survival And Growth

Abstract Formation of new vessels during development and in the mature mammal generally proceeds through angiogenesis. Although a variety of molecules and signaling pathways are known to underlie endothelial cell sprouting and remodeling during angiogenesis, many aspects of this complex process remain unexplained. Here we show that the transmembrane semaphorin6A (Sema6A) is expressed in endothelial cells, and regulates endothelial cell survival and growth by modulating the expression and signaling of VEGFR2, which is known to maintain endothelial cell viability by autocrine VEGFR signaling. The silencing of Sema6A in primary endothelial cells promotes cell death that is not rescued by exogenous VEGF-A or FGF2, attributable to the loss of prosurvival signaling from endogenous VEGF. Analyses of mouse tissues demonstrate that Sema6A is expressed in angiogenic and remodeling vessels. Mice with null mutations of Sema6A exhibit significant defects in hyaloid vessels complexity associated with increased endothelial cell death, and in retinal vessels development that is abnormally reduced. Adult Sema6A-null mice exhibit reduced tumor, matrigel, and choroidal angiogenesis compared with controls. Sema6A plays important roles in development of the nervous system. Here we show that it also regulates vascular development and adult angiogenesis.

Epidermal growth factor-like domain 7 protects endothelial cells from hyperoxia-induced cell death

2008 ◽  
Vol 294 (1) ◽  
pp. L17-L23 ◽  
Author(s):  
Dong Xu ◽  
Ricardo E. Perez ◽  
Ikechukwu I. Ekekezie ◽  
Angels Navarro ◽  
William E. Truog
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Lung Injury ◽  
Neonatal Rat ◽  
Apoptosis Pathway ◽  
Endothelial Cell Death ◽  
Epidermal Growth

Hyperoxia is one of the major contributors to the development of bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants. Emerging evidence suggests that the arrested lung development of BPD is associated with pulmonary endothelial cell death and vascular dysfunction resulting from hyperoxia-induced lung injury. A better understanding of the mechanism of hyperoxia-induced endothelial cell death will provide critical information for the pathogenesis and therapeutic development of BPD. Epidermal growth factor-like domain 7 (EGFL7) is a protein secreted from endothelial cells. It plays an important role in vascular tubulogenesis. In the present study, we found that Egfl7 gene expression was significantly decreased in the neonatal rat lungs after hyperoxic exposure. The Egfl7 expression was returned to near normal level 2 wk after discounting oxygen exposure during recovery period. In cultured human endothelial cells, hyperoxia also significantly reduced Egfl7 expression. These observations suggest that diminished levels of Egfl7 expression might be associated with hyperoxia-induced endothelial cell death and lung injury. When we overexpressed human Egfl7 ( hEgfl7) in EA.hy926 human endothelial cell line, we found that hEgfl7 overexpression could partially block cytochrome c release from mitochondria and decrease caspase-3 activation. Further Western blotting analyses showed that hEgfl7 overexpression could reduce expression of a proapoptotic protein, Bax, and increase expression of an antiapoptotic protein, Bcl-xL. Theses findings indicate that hEGFL7 may protect endothelial cell from hyperoxia-induced apoptosis by inhibition of mitochondria-dependent apoptosis pathway.

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