scholarly journals Endothelial endoglin is involved in inflammation: role in leukocyte adhesion and transmigration

Blood ◽  
2013 ◽  
Vol 121 (2) ◽  
pp. 403-415 ◽  
Author(s):  
Elisa Rossi ◽  
Francisco Sanz-Rodriguez ◽  
Nelida Eleno ◽  
Annette Düwell ◽  
Francisco J. Blanco ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Leukocyte Adhesion ◽  
Leukocyte Trafficking ◽  
Inhibitory Antibody ◽  
Integrin Α5β1 ◽  
Rgd Peptides ◽  
Leukocyte Transmigration ◽  
Soluble Endoglin ◽  
Chemokine Cxcl12

Abstract Human endoglin is an RGD-containing transmembrane glycoprotein identified in vascular endothelial cells. Although endoglin is essential for angiogenesis and its expression is up-regulated in inflammation and at sites of leukocyte extravasation, its role in leukocyte trafficking is unknown. This function was tested in endoglin heterozygous mice (Eng+/−) and their wild-type siblings Eng+/+ treated with carrageenan or LPS as inflammatory agents. Both stimuli showed that inflammation-induced leukocyte transendothelial migration to peritoneum or lungs was significantly lower in Eng+/− than in Eng+/+ mice. Leukocyte transmigration through cell monolayers of endoglin transfectants was clearly enhanced in the presence of endoglin. Coating transwells with the RGD-containing extracellular domain of endoglin, enhanced leukocyte transmigration, and this increased motility was inhibited by soluble endoglin. Leukocytes stimulated with CXCL12, a chemokine involved in inflammation, strongly adhered to endoglin-coated plates and to endoglin-expressing endothelial cells. This endoglin-dependent adhesion was abolished by soluble endoglin, RGD peptides, the anti-integrin α5β1 inhibitory antibody LIA1/2 and the chemokine receptor inhibitor AMD3100. These results demonstrate for the first time that endothelial endoglin interacts with leukocyte integrin α5β1 via its RGD motif, and this adhesion process is stimulated by the inflammatory chemokine CXCL12, suggesting a regulatory role for endoglin in transendothelial leukocyte trafficking.

scholarly journals Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells

2018 ◽  
Author(s):  
Yoshiki Higashijima ◽  
Yusuke Matsui ◽  
Teppei Shimamura ◽  
Shuichi Tsutsumi ◽  
Ryo Nakaki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Leukocyte Adhesion ◽  
List Type ◽  
Chromosome Conformation ◽  
Histone Marks ◽  
Tnf Α ◽  
Simultaneous Inhibition ◽  
Adhesive Interactions

SUMMARYLysine 9 di-methylation and lysine 27 tri-methylation of histone H3 (H3K9me2 and H3K27me3) are generally linked to gene repression. However, the functions of repressive histone methylation dynamics during inflammatory responses remain enigmatic. We found that tumor necrosis factor (TNF)-α rapidly induces the co-occupancy of lysine demethylases 7A (KDM7A) and 6A (UTX) with nuclear factor kappa-B (NF-κB) recruited elements in human endothelial cells. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and both are required for activation of NF-κB-dependent inflammatory genes. Chromosome conformation capture-based methods demonstrated increased interactions between TNF-α-induced super enhancers at NF-κB-relevant loci, coinciding with KDM7A- and UTX-recruitment. Simultaneous inhibition of KDM7A and UTX significantly reduced leukocyte adhesion in mice, establishing the biological and potential translational relevance of this mechanism. Collectively, these findings suggest that rapid erasure of repressive histone marks by KDM7A and UTX is essential for NF-κB-dependent regulation of genes that control inflammatory responses of endothelial cells.HIGHLIGHTSKDM7A and UTX cooperatively control NF-κB-dependent transcription in vascular endothelial cells.Demethylation of repressive histone marks by KDM7A and UTX is critical for early inflammatory responses.KDM7A and UTX are associated with TNF-α-induced looping of super enhancers.Pharmacological inhibition of KDM7A and UTX reduces leukocyte adhesive interactions with endothelial cells in mice.

Heparin-Like Glycosaminoglycans Inhibit Leukocyte Adhesion to Endotoxin-Activated Human Vascular Endothelial Cells under Nonstatic Conditions

1996 ◽  
Vol 28 (6) ◽  
pp. 428-435 ◽  
Author(s):  
N. Kitamura ◽  
M. Yamaguchi ◽  
K. Shimabukuro ◽  
M. Miyasaka ◽  
H. Nakano ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Leukocyte Adhesion ◽  
Vascular Endothelial

Diarylheptanoids suppress expression of leukocyte adhesion molecules on human vascular endothelial cells

2000 ◽  
Vol 404 (3) ◽  
pp. 375-385 ◽  
Author(s):  
Ryuta Yamazaki ◽  
Hiroshi Hatano ◽  
Ritsuo Aiyama ◽  
Takeshi Matsuzaki ◽  
Shusuke Hashimoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Vascular Endothelial Cells ◽  
Leukocyte Adhesion ◽  
Vascular Endothelial ◽  
Leukocyte Adhesion Molecules

Antiphospholipid Antibodies Activate Vascular Endothelial Cells

Lupus ◽  
1996 ◽  
Vol 5 (5) ◽  
pp. 440-441 ◽  
Author(s):  
R Simantov ◽  
SK Lo ◽  
A Gharavi ◽  
LR Sammaritano ◽  
JE Salmon ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Antiphospholipid Antibodies ◽  
Vascular Endothelial Cells ◽  
Leukocyte Adhesion ◽  
Fetal Loss ◽  
Endothelial Activation ◽  
Vascular Endothelial ◽  
Endothelial Surface ◽  
Endotoxin Contamination ◽  
Leukocyte Adhesion Molecules

Antiphospholipid antibodies (aPL) are associated with a syndrome of arterial and venous thrombosis and recurrent fetal loss. We have shown that IgG purified from patients with aPL activate vascular endothelial cells (EC), converting the steady-state, non-thrombotic endothelial surface to a pro-thrombotic state. The aPL-activated EC are characterized by the expression of leukocyte adhesion molecules, including ICAM-1, VCAM, and E-selectin. EC activation is dependent upon the presence of β2-GP-I, a cofactor necessary for anticardiolipin reactivity. In addition, EC activation is not attributable to endotoxin contamination, Fc receptor interactions, or immune complexes, but rather is the result of the specific anticardiolipin reactivity of the IgG. Endothelial activation by aPL may be an important mechanism by which these antibodies cause a hypercoagulable state.

scholarly journals Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis

2017 ◽  
Vol 115 (1) ◽  
pp. 133-138 ◽  
Author(s):  
Yi-Ting Yeh ◽  
Ricardo Serrano ◽  
Joshua François ◽  
Jeng-Jiann Chiu ◽  
Yi-Shuan Julie Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Temporal Evolution ◽  
Vascular Endothelial Cells ◽  
Three Dimensional ◽  
Innate Immune ◽  
Cell Junctions ◽  
Vascular Endothelial ◽  
Endothelial Monolayer ◽  
Leukocyte Transmigration ◽  
The Matrix

Leukocyte transmigration across vessel walls is a critical step in the innate immune response. Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has been hypothesized that VECs facilitate paracellular diapedesis by opening their cell–cell junctions in response to the presence of an adhering leukocyte. However, it is unclear how leukocytes interact mechanically with VECs to open the VEC junctions and migrate across the endothelium. In this study, we measured the spatial and temporal evolution of the 3D traction stresses generated by the leukocytes and VECs to elucidate the sequence of mechanical events involved in paracellular diapedesis. Our measurements suggest that the contractile stresses exerted by the leukocytes and the VECs can separately perturb the junctional tensions of VECs to result in the opening of gaps before the initiation of leukocyte transmigration. Decoupling the stresses exerted by the transmigrating leukocytes and the VECs reveals that the leukocytes actively contract the VECs to open a junctional gap and then push themselves across the gap by generating strong stresses that push into the matrix. In addition, we found that diapedesis is facilitated when the tension fluctuations in the VEC monolayer were increased by proinflammatory thrombin treatment. Our findings demonstrate that diapedesis can be mechanically regulated by the transmigrating leukocytes and by proinflammatory signals that increase VEC contractility.

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