Interactions of Aspergillus fumigatus with endothelial cells: internalization, injury, and stimulation of tissue factor activity

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2143-2149 ◽  
Author(s):  
Leila M. Lopes Bezerra ◽  
Scott G. Filler
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Tissue Factor ◽  
Cell Injury ◽  
Factor Activity ◽  
Endothelial Cell Injury ◽  
Tissue Factor Activity ◽  
Stimulation Of

Abstract Invasive aspergillosis causes significant mortality among patients with hematologic malignancies. This infection is characterized by vascular invasion and thrombosis. To study the pathogenesis of invasive aspergillosis, we investigated the interactions of Aspergillus fumigatus conidia and hyphae with endothelial cells in vitro. We found that both forms of the organism induced endothelial cell microfilament rearrangement and subsequent endocytosis. Conidia were endocytosed 2-fold more avidly than hyphae, and endocytosis was independent of fungal viability. Endocytosed conidia and hyphae caused progressive endothelial cell injury after 4 hours of infection. Live conidia induced more endothelial cell injury than did live hyphae. However, endothelial cell injury caused by conidia was dependent on fungal viability, whereas injury caused by hyphae was not, indicating that conidia and hyphae injure endothelial cells by different mechanisms. Neither live nor killed conidia increased tissue factor activity of endothelial cells. In contrast, both live and killed hyphae stimulated significant endothelial cell tissue factor activity, as well as the expression of tissue factor antigen on the endothelial cell surface. These results suggest that angioinvasion and thrombosis caused by A fumigatus hyphae in vivo may be due in part to endothelial cell invasion, induction of injury, and stimulation of tissue factor activity.

scholarly journals Plasmin enhances cell surface tissue factor activity in mesothelial and endothelial cells

2009 ◽  
Vol 7 (1) ◽  
pp. 121-131 ◽  
Author(s):  
H. KOTHARI ◽  
G. KAUR ◽  
S. SAHOO ◽  
S. IDELL ◽  
L. V. M. RAO ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Tissue Factor ◽  
Factor Activity ◽  
Tissue Factor Activity

scholarly journals Tissue factor promotes activation of coagulation and inflammation in a mouse model of sickle cell disease

Blood ◽  
2012 ◽  
Vol 120 (3) ◽  
pp. 636-646 ◽  
Author(s):  
Pichika Chantrathammachart ◽  
Nigel Mackman ◽  
Erica Sparkenbaugh ◽  
Jian-Guo Wang ◽  
Leslie V. Parise ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Sickle Cell Disease ◽  
Tissue Factor ◽  
Sickle Cell ◽  
Plasma Levels ◽  
Cell Injury ◽  
Vascular Inflammation ◽  
Cell Disease ◽  
Endothelial Cell Injury ◽  
Cell Adhesion Molecule 1

Abstract Sickle cell disease (SCD) is associated with a complex vascular pathophysiology that includes activation of coagulation and inflammation. However, the crosstalk between these 2 systems in SCD has not been investigated. Here, we examined the role of tissue factor (TF) in the activation of coagulation and inflammation in 2 different mouse models of SCD (BERK and Townes). Leukocytes isolated from BERK mice expressed TF protein and had increased TF activity compared with control mice. We found that an inhibitory anti-TF antibody abrogated the activation of coagulation but had no effect on hemolysis or anemia. Importantly, inhibition of TF also attenuated inflammation and endothelial cell injury as demonstrated by reduced plasma levels of IL-6, serum amyloid P, and soluble vascular cell adhesion molecule-1. In addition, we found decreased levels of the chemokines MCP-1 and KC, as well as myeloperoxidase in the lungs of sickle cell mice treated with the anti-TF antibody. Finally, we found that endothelial cell-specific deletion of TF had no effect on coagulation but selectively attenuated plasma levels of IL-6. Our data indicate that different cellular sources of TF contribute to activation of coagulation, vascular inflammation, and endothelial cell injury. Furthermore, it appears that TF contributes to these processes without affecting intravascular hemolysis.

scholarly journals Heterogeneous regulation of constitutive thrombomodulin or inducible tissue-factor activities on the surface of human saphenous-vein endothelial cells in culture following stimulation by interleukin-1, tumour necrosis factor, thrombin or phorbol ester

1991 ◽  
Vol 273 (3) ◽  
pp. 679-684 ◽  
Author(s):  
G Archipoff ◽  
A Beretz ◽  
J M Freyssinet ◽  
C Klein-Soyer ◽  
C Brisson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Saphenous Vein ◽  
Tumour Necrosis ◽  
Protein C ◽  
Interleukin 1 ◽  
Factor Activity ◽  
Human Saphenous Vein ◽  
Tissue Factor Activity ◽  
Necrosis Factor

Thrombomodulin and tissue-factor activities were measured on the surface of confluent human saphenous-vein endothelial cells (HSVEC) cultivated in 96-multiwell plates. Thrombomodulin activity was measured in the presence of purified human thrombin (2.2 nM) and protein C (65 nM). Tissue-factor activity was measured with purified human Factor VII (5 nM) and Factor X (400 nM). Generated activated protein C and Factor Xa released in the supernatant were assayed with chromogenic substrates. Resting cells exhibited significant thrombomodulin activity, but no detectable tissue-factor activity. After 4 h of preincubation with tumour necrosis factor (TNF, 22-2200 pM), interleukin-1 (IL-1, 5.7-570 nM) or phorbol myristate acetate (PMA, 1.61-161 nM) there was an increase in tissue-factor activity and a concomitant decrease in thrombomodulin activity. However, the extent of both responses varied according to the nature of the stimulus. Thrombin (0.44-44 nM) also induced an increase in tissue-factor activity, but had no effect on thrombomodulin activity. Kinetic studies showed that for all stimuli the increase in tissue factor was transient, reaching a maximum after 4-8 h of preincubation with the stimulating agent and returning to normal values after 24 h. IL-1 and TNF induced a time-dependent decrease in thrombomodulin, by respectively 47% and 67% of control values after 24 h. However, PMA induced only a transient down-regulation of thrombomodulin, full activity being recovered after 18 h. Hence this simultaneous assay system, using intact HSVEC and purified human coagulation factors, enabled us to observe that the regulation of thrombin generation could be diversely affected by various substances known to stimulate the endothelium. This suggests that the simultaneous and opposite modulation of these proteins does not represent an unified response of the endothelial cells to procoagulant stimuli. These results also confirm the absence of effect of thrombin on the expression of thrombomodulin on the cell surface.

Peptide5 attenuates rtPA related brain microvascular endothelial cells reperfusion injury via the Wnt/β-catenin signalling pathway

2021 ◽  
Vol 18 ◽  
Author(s):  
Weimin Ren ◽  
Chuyi Huang ◽  
Heling Chu ◽  
Yuping Tang ◽  
Xiaobo Yang
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Endothelial Cell ◽  
Cell Injury ◽  
Time Window ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Endothelial Cell Injury ◽  
Endothelial Cell Death ◽  
Therapeutic Time Window

Aims: Brain vascular endothelial cell dysfunction after rtPA treatment is a significant factor associated with poor prognosis, suggesting that alleviation of rtPA-related endothelial cell injury may represent a potential beneficial strategy along with rtPA thrombolysis. Background: Thrombolysis with recombinant tissue plasminogen activator (rtPA) is beneficial for acute ischemic stroke but may increase the risk of hemorrhagic transformation (HT), which is considered ischemia-reperfusion injury. The underlying reason may contribute to brain endothelial injury and dysfunction related to rtPA against ischemic stroke. As previous studies have demonstrated that transiently blocked Cx43 using peptide5 (Cx43 mimetic peptide) during retinal ischemia reduced vascular leakage, it is necessary to know whether this might help decrease side effect of rtPA within the therapeutic time window. Objective: This study aims to investigate the effects of peptide5 on rtPA-related cell injury during hypoxia/reoxygenation (H/R) within the therapeutic time window. Methods: In this study, we established a cell hypoxia/reoxygenation H/R model in cultured primary rat brain microvascular endothelial cells (RBMECs) and evaluated endothelial cell death and permeability after rtPA treatment with or without transient peptide5. In addition, we also investigated the potential signaling pathway to explore the underlying mechanisms preliminarily. Results: The results showed that peptide5 inhibited rtPA-related endothelial cell death and permeability. It also slightly increased tight junction (ZO-1, occluding, claudin-5) and β-catenin mRNA expression, demonstrating that peptide5 might attenuate endothelial cell injury by regulating the Wnt/β-catenin pathway. The following bioinformatic exploration from the GEO dataset GSE37239 was also consistent with our findings. Conclusion: This study showed that the application of peptide5 maintained cell viability and permeability associated with rtPA treatment, revealing a possible pathway that could be exploited to limit rtPA-related endothelial cell injury during ischemic stroke. Furthermore, the altered Wnt/β-catenin signaling pathway demonstrated that signaling pathways associated with Cx43 might have potential applications in the future. This study may provide a new way to attenuate HT and assist the application of rtPA in ischemic stroke.

scholarly journals Omentin-1 Ameliorated Free Fatty Acid-Induced Impairment in Proliferation, Migration, and Inflammatory States of HUVECs

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yubin Chen ◽  
Fen Liu ◽  
Fei Han ◽  
Lizhi Lv ◽  
Can-e Tang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fatty Acid ◽  
Endothelial Cell ◽  
Free Fatty Acid ◽  
Cell Injury ◽  
Umbilical Vein ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Counting ◽  
Endothelial Cell Injury ◽  
Umbilical Vein Endothelial Cells

Objectives. Endothelial cell injury is a critical pathological change during the development of atherosclerosis. Here, we explored the effect of omentin-1 on free fatty acid- (FFA-) induced endothelial cell injury. Methods. An FFA-induced endothelial cell injury model was established to investigate the role of omentin-1 in this process. Cell proliferation was analyzed with the Cell Counting Kit assay and flow cytometry. Scratch and transwell assays were used to evaluate cell migration. Factors secreted by endothelial cells after injury were detected by western blotting, reverse-transcription quantitative polymerase chain reaction, and cellular fluorescence assay. Results. Omentin-1 rescued the FFA-induced impaired proliferation and migration capabilities of human umbilical vein endothelial cells (HUVECs). It decreased the number of THP-1 cells attached to HUVECs in response to injury and inhibited the FFA-induced proinflammatory state of HUVECs. Conclusion. Omentin-1 could partly ameliorate FFA-induced endothelial cell injury.

Priming effect of adrenic acid (22:4(n-6)) on tissue factor activity expressed by thrombin-stimulated endothelial cells

1992 ◽  
Vol 95 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Brigitte Tardy ◽  
Jean-Claude Bordet ◽  
Micheline Berruyer ◽  
Patrick Ffrench ◽  
Marc Dechavanne
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Priming Effect ◽  
Factor Activity ◽  
Tissue Factor Activity ◽  
Adrenic Acid

scholarly journals Induction of tissue factor activity in endothelial cells and monocytes by a modified form of albumin present in normal human plasma

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2888-2895
Author(s):  
KJ Faucette ◽  
CJ Parker ◽  
T McCluskey ◽  
NJ Bernshaw ◽  
GM Rodgers
Keyword(s):  
Endothelial Cells ◽  
Human Plasma ◽  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Factor Activity ◽  
Normal Human Plasma ◽  
Human Endothelial Cells ◽  
Tissue Factor Activity ◽  
Factor Expression ◽  
Normal Human

Molecules that induce tissue factor expression by responsive cells such as endothelial cells and monocytes may be important in the regulation of hemostasis and, perhaps, in mediating certain hemostatic disorders. A constituent of normal human plasma capable of inducing tissue factor activity in human endothelial cells and monocytes has been isolated and identified as a derivative of, or modification associated with albumin. Procoagulant albumin caused a concentration-dependent induction of tissue factor expression by human endothelial cells, but bovine endothelial cells were unresponsive. The dose-response curve developed a plateau phase, indicating that the capacity of endothelial cells to respond to the stimulus was finite. The maximum response induced by the procoagulant albumin was similar to that observed for maximally effective concentrations of endotoxin, interleukin-1, and tumor necrosis factor. Time-course studies showed that procoagulant albumin produced peak activity in 4 to 6 hours. Identification of a procoagulant form of albumin in normal human plasma suggests a potential role for this constituent in regulation of hemostasis.

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