scholarly journals Methyl mercury triggers endothelial leukocyte adhesion and increases expression of cell adhesion molecules and chemokines

2021 ◽  
pp. 153537022110338
Author(s):  
Joshua Fowler ◽  
Martin Tsz-Ki Tsui ◽  
Jessica Chavez ◽  
Safeera Khan ◽  
Hassan Ahmed ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Methyl Mercury ◽  
Leukocyte Adhesion ◽  
Flow Cytometric Analysis ◽  
Toxic Metal ◽  
Initial Step ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Monocyte Chemoattractant Protein 1

Cardiovascular disease is the leading cause of morbidity, mortality, and health care costs in the USA, and around the world. Among the various risk factors of cardiovascular disease, environmental and dietary exposures to methyl mercury, a highly toxic metal traditionally labeled as a neurotoxin, have been epidemiologically linked to human cardiovascular disease development. However, its role in development and promotion of atherosclerosis, an initial step in more immediately life-threatening cardiovascular diseases, remains unclear. This study was conducted to examine the role that methyl mercury plays in the adhesion of monocytes to human microvascular endothelial cells (HMEC-1), and the underlying mechanisms. Methyl mercury treatment significantly induced the adhesion of monocyte to HMEC-1 endothelial cells, a critical step in atherosclerosis, while also upregulating the expression of proinflammatory cytokines interleukin-6, interleukin-8. Further, methyl mercury treatment also upregulated the chemotactic cytokine monocyte chemoattractant protein-1 and intercellular adhesion molecule-1. These molecules are imperative for the firm adhesion of leukocytes to endothelial cells. Additionally, our results further demonstrated that methyl mercury stimulated a significant increase in NF-κB activation. These findings suggest that NF-κB signaling pathway activation by methyl mercury is an important factor in the binding of monocytes to endothelial cells. Finally, by using flow cytometric analysis, methyl mercury treatment caused a significant increase in necrotic cell death only at higher concentrations without initiating apoptosis. This study provides new insights into the molecular actions of methyl mercury that can lead to endothelial dysfunction, inflammation, and subsequent atherosclerotic development.

scholarly journals Key Proteins Involved in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity

2018 ◽  
Vol 45 (2) ◽  
pp. 429-445 ◽  
Author(s):  
Anita Dittrich ◽  
Daniela Grimm ◽  
Jayashree Sahana ◽  
Johann Bauer ◽  
Marcus Krüger ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Cell Structure ◽  
Three Dimensional ◽  
Cardiovascular Complications ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Multicellular Spheroids ◽  
Monocyte Chemoattractant Protein 1 ◽  
Molecular Approaches

Background/Aims: Cardiovascular complications are common in astronauts returning from a prolonged spaceflight. These health problems might be driven by complex modulations of gene expression and protein synthesis in endothelial cells (ECs). Studies on the influence of microgravity on phenotype, growth pattern and biological processes of ECs can help to understand these complications. Methods: We exposed ECs (EA.hy926) to a Random Positioning Machine (RPM). Proteins associated with cell structure, angiogenesis and endothelial dysfunction were investigated in distinct pools of multicellular spheroids (MCS), adherent cells (AD) and tubular structures (TS) formed after a 35-day RPM-exposure. Results: Combining morphological and molecular approaches, we found AD, MCS and TS with changes in the synthesis and release of proteins involved in three-dimensional growth. Fibronectin and monocyte chemoattractant protein-1 (MCP-1) mRNAs and protein contents were elevated along with an increased secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, MCP-1, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL) and regulated on activation, normal T cell expressed and secreted (RANTES) proteins in the culture supernatant as determined by multianalyte profiling technology. Together they form a network of interaction. Conclusions: These results show that a prolonged RPM-exposure of ECs induced TS and MCS formation. The factors VEGF, NGAL, IL-6, IL-8, MCP-1, VCAM-1, ICAM-1, fibronectin and RANTES seem to be affected when gravity is omitted.

Lysophosphatidic Acid Activates Nuclear Factor Kappa B and Induces Proinflammatory Gene Expression in Endothelial Cells

1999 ◽  
Vol 82 (11) ◽  
pp. 1532-1537 ◽  
Author(s):  
Simon Robson ◽  
Volker Nehls ◽  
Alois Palmetshofer
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Lysophosphatidic Acid ◽  
Nuclear Factor Kappa B ◽  
Intercellular Adhesion Molecule ◽  
Nuclear Factor ◽  
Intercellular Adhesion Molecule 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Nuclear Factor Kappa ◽  
Activated Platelets

SummaryThe cellular phospholipid, lysophosphatidic acid (LPA), released by activated platelets and fibroblasts or, at high levels, from ovarian and cervical carcinomas is a powerful serum mitogen that may modulate several signaling pathways in endothelial cells (EC). Hence, LPA could function in a paracrine manner during EC-platelet interactions at sites of vascular injury.Here, we demonstrate activation of the transcription factor nuclear factor kappa B (NF-κB) in EC following exposure to LPA. EC activation was further characterized by increased levels of mRNA transcripts encoding E-selectin, Intercellular Adhesion Molecule-1, Interleukin-8 and Monocyte Chemoattractant Protein-1. These effects were inhibited by preincubating EC either in the presence of mepacrine (to block phospholipase A2) or of pertussis toxin (to increase ADP-ribosylation of Gi proteins). No inhibition was observed in the presence of putative LPA receptor antagonists suramin or thrombospondin.LPA induces a proinflammatory activation of endothelial cells that (i) involves Gi proteins; (ii) depends on phospholipase A2 activity; (iii) is associated with the activation of NF-κB and (iv) results in increased expression of proinflammatory genes. We propose that LPA release by activated platelets may directly modulate vascular inflammatory responses. Abbreviations: EC, endothelial cells; LPA, lysophosphatidic acid; NF-κB, nuclear factor kappa B; PA, phosphatidic acid; IL-8, interleukin-8; MCP-1, monocyte chemoattractant protein-1, ICAM-1, intercellular adhesion molecule-1, vascular adhesion molecule-1; GAPDH, glycerol aldehyde phosphate dehydrogenase; MAPK, mitogen activated kinase, MEK, MAPK kinase, PAEC, porcine aortic EC.

scholarly journals Role of Hyphal Formation in Interactions ofCandida albicans with Endothelial Cells

2000 ◽  
Vol 68 (6) ◽  
pp. 3485-3490 ◽  
Author(s):  
Quynh T. Phan ◽  
Paul H. Belanger ◽  
Scott G. Filler
Keyword(s):  
Endothelial Cells ◽  
Leukocyte Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Proinflammatory Response ◽  
Regulatory Pathways ◽  
Ofcandida Albicans ◽  
Hyphal Formation

ABSTRACT The ability to change from yeast to hyphal morphology is a major virulence determinant of Candida albicans. Mutants with defined defects in filamentation regulatory pathways have reduced virulence in mice. However, is it poorly understood why hyphal formation is critical for C. albicans to cause hematogenously disseminated infections. We used recently constructed mutants to examine the role of hyphal formation in the interactions ofC. albicans with endothelial cells in vitro. These interactions included the ability of the mutants to invade and injure endothelial cells. Because the formation of hyphae may influence the host inflammatory response to C. albicans, we also investigated the capacity of these mutants to stimulate endothelial cells to express E-selectin and intercellular adhesion molecule 1. We infected endothelial cells with C. albicans strains containing homozygous null mutations in the following filamentation regulatory genes: CLA4, CPH1,EFG1, and TUP1. Whereas the wild-type strain formed true hyphae on endothelial cells, we found that neither the Δefg1 nor the Δcph1 Δefg1double mutant germinated. The Δtup1 mutant formed only pseudohyphae. We also found that the Δefg1, Δcph1 Δefg1, and Δtup1 mutants had significantly reduced capacities to invade and injure endothelial cells. Therefore, Efg1p and Tup1p contribute to virulence by regulating hyphal formation and the factors that enable C. albicans to invade and injure endothelial cells. With the exception of the Δcph1 Δefg1 mutant, all other mutants stimulated endothelial cells to express at least one of the leukocyte adhesion molecules. Therefore, the combined activities of Cph1p and Efg1p are required for C. albicans to stimulate a proinflammatory response in endothelial cells.

Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes by downregulating VCAM-1 expression

1994 ◽  
Vol 267 (3) ◽  
pp. C679-C687 ◽  
Author(s):  
J. Ando ◽  
H. Tsuboi ◽  
R. Korenaga ◽  
Y. Takada ◽  
N. Toyama-Sorimachi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Adhesion Molecule ◽  
Flow Cytometric Analysis ◽  
Flow Chamber ◽  
Intercellular Adhesion Molecule ◽  
Mrna Levels ◽  
Intercellular Adhesion Molecule 1 ◽  
Rate Dependent ◽  
Stress Dependent

Monolayers of endothelial cells (EC) cultured from mouse lymph nodes were exposed to controlled levels of shear stress (0-7.1 dyn/cm2) in a parallel plate flow chamber, and binding between the flow-loaded EC and mouse lymph node-derived lymphocytes was assayed. A large number of lymphocytes adhered to the stationary control EC, but in EC exposed to a shear stress of 1.5 dyn/cm2 for 6 h, the adhesion decreased to 68.8 +/- 12.8% (SD; n = 19) of control (n = 29, P < 0.001). The decrease in adhesion induced by flow loading was time and shear stress dependent and reversible. Treatment of stationary EC with a monoclonal antibody (MAb) to vascular cell adhesion molecule-1 (VCAM-1) reduced the adhesion to 70.6 +/- 11.5% (n = 19) of control (P < 0.001), whereas MAb to CD44 and to intercellular adhesion molecule-1 had no effect on it. Flow cytometric analysis revealed that the amount of VCAM-1 expressed on the cell surface was decreased to 48.5 +/- 15.8% (n = 6) of control by flow loading (P < 0.001). Flow loading experiments using two perfusates with different viscosities demonstrated that the decrease in VCAM-1 expression due to flow was shear stress rather than shear rate dependent. The detection of mRNA by reverse transcriptase-polymerase chain reaction showed that VCAM-1 mRNA levels were markedly depressed in EC exposed to flow loading.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Insulin Inhibits NFκB and MCP-1 Expression in Human Aortic Endothelial Cells

2001 ◽  
Vol 86 (1) ◽  
pp. 450-453 ◽  
Author(s):  
Ahmad Aljada ◽  
Husam Ghanim ◽  
Rana Saadeh ◽  
Paresh Dandona
Keyword(s):  
Endothelial Cells ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Aortic Endothelial Cells ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

In view of our recent demonstration that insulin inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) and the fact that ICAM-1 expression is known to be modulated by nuclear factor-κB (NFκB), we have now investigated whether insulin inhibits intranuclear NFκB binding activity. We have also investigated whether insulin inhibits the pro-inflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), which attracts leucocytes to the inflamed sites and is also regulated by NFκB. Insulin was incubated with cultured human aortic endothelial cells (HAEC) at 0, 100 and 1000μ U/mL. Intranuclear NFκB binding activity was suppressed by approximately 45% at 100 μU/mL and by 60% at 1000 μU/mL (p&lt; 0.05). MCP-1 mRNA expression was also suppressed by 47% at 100μ U/mL and by 79% at 1000 μU/mL (p &lt; 0.05). We conclude that insulin at physiologically relevant concentrations exerts an inhibitory effect on the cardinal pro-inflammatory transcription factor NFκB and the pro-inflammatory chemokine MCP-1; these effects suggest an anti-inflammatory and potential anti-atherogenic effects of insulin.

scholarly journals The Cytolytically Inactive Terminal Complement Complex Activates Endothelial Cells to Express Adhesion Molecules and Tissue Factor Procoagulant Activity

1997 ◽  
Vol 185 (9) ◽  
pp. 1619-1628 ◽  
Author(s):  
Francesco Tedesco ◽  
Mario Pausa ◽  
Ermanno Nardon ◽  
Martino Introna ◽  
Alberto Mantovani ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Membrane Attack Complex ◽  
Procoagulant Activity ◽  
Biologically Active ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

The membrane attack complex of complement (C) in sublytic concentrations stimulates endothelial cells (EC) to express adhesion molecules and to release biologically active products. We have examined the ability of a cytolytically inactive form of this complex, which is incapable of inserting into the cell membrane, to upregulate the expression of adhesion molecules and of tissue factor (TF) procoagulant activity. The inactive terminal C complex (iTCC) was prepared by mixing C5b6, C7, C8, and C9 and was purified by fast protein liquid chromatography on a Superose 12 column. Binding of this complex to EC was found to be dose dependent and was inhibited by anti-C9 antibodies, as assessed both by ELISA using an mAb anti-C9 neoantigen and by measuring cell-bound 125I-labeled iTCC. Exposure of EC to iTCC resulted in a dose- and time-dependent expression of endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 accompanied by increased levels of the corresponding mRNA, but not in the rapid expression of P-selectin. Inactive TCC also induced increased TF activity evaluated by a chromogenic assay that measures the formation of factor Xa. These effects were inhibited by anti-C9 antibodies. The data support the conclusion that iTCC may induce proinflammatory and procoagulant activities on EC.

Sign in / Sign up

Export Citation Format

Share Document