Faculty Opinions recommendation of JAM-L-mediated leukocyte adhesion to endothelial cells is regulated in cis by alpha4beta1 integrin activation.

Junctional adhesion molecules (JAMs) are endothelial and epithelial adhesion molecules involved in the recruitment of circulating leukocytes to inflammatory sites. We show here that JAM-L, a protein related to the JAM family, is restricted to leukocytes and promotes their adhesion to endothelial cells. Cis dimerization of JAM-L is required to engage in heterophilic interactions with its cognate counter-receptor CAR (coxsackie and adenovirus receptor). Interestingly, JAM-L expressed on neutrophils binds CAR independently of integrin activation. However, on resting monocytes and T lymphocytes, which express the integrin VLA-4, JAM-L molecules engage in complexes with VLA-4 and mainly accumulate in their monomeric form. Integrin activation is required for the dissociation of JAM-L–VLA-4 complexes and the accumulation of functional JAM-L dimers, which indicates that the leukocyte integrin VLA-4 controls JAM-L function in cis by controlling its dimerization state. This provides a mechanism through which VLA-4 and JAM-L functions are coordinately regulated, allowing JAM-L to strengthen integrin-dependent adhesion of leukocytes to endothelial cells.

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JAM-L–mediated leukocyte adhesion to endothelial cells is regulated in cis by a4b1 integrin activation

Journal of Experimental Medicine ◽

10.1084/jem20513oia29 ◽

2008 ◽

Vol 205 (13) ◽

pp. i29-i29

Author(s):

Anny-Claude Luissint ◽

Pierre G. Lutz ◽

David A. Calderwood ◽

Pierre-Olivier Couraud ◽

Sandrine Bourdoulous

Keyword(s):

Endothelial Cells ◽

Leukocyte Adhesion ◽

Integrin Activation ◽

In Cis

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Faculty Opinions recommendation of Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1159384.619738 ◽

2009 ◽

Author(s):

Thomas Egelhoff

Keyword(s):

Endothelial Cells ◽

Leukocyte Adhesion

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3-Deazaadenosine inhibits thrombin-stimulated platelet-derived growth factor production and endothelial-leukocyte adhesion molecule-1-mediated monocytic cell adhesion in human aortic endothelial cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)50434-3 ◽

1992 ◽

Vol 267 (13) ◽

pp. 9376-9382

Author(s):

R Shankar ◽

C.A. de la Motte ◽

P.E. DiCorleto

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Leukocyte Adhesion ◽

Platelet Derived Growth Factor ◽

Monocytic Cell ◽

Aortic Endothelial Cells ◽

Leukocyte Adhesion Molecule ◽

Growth Factor Production ◽

Endothelial Leukocyte Adhesion Molecule ◽

Human Aortic Endothelial Cells

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Relationship between tissue factor expression and deposition of fibrin, platelets, and leukocytes on cultured endothelial cells under venous blood flow conditions

Blood ◽

10.1182/blood.v81.8.2050.2050 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2050-2058 ◽

Cited By ~ 56

Author(s):

D Kirchhofer ◽

KS Sakariassen ◽

M Clozel ◽

TB Tschopp ◽

P Hadvary ◽

...

Keyword(s):

Endothelial Cells ◽

Tissue Factor ◽

Cross Section ◽

Leukocyte Adhesion ◽

Venous Blood ◽

Cell Contact ◽

Venous Blood Flow ◽

Necrosis Factor Alpha ◽

Endothelial Surface ◽

Platelet Aggregates

Abstract Endothelial cell-mediated coagulation and leukocyte adhesion are processes that might be connected by the generation of thrombin. To examine the interaction of procoagulant and proadhesive activity, cultures of endothelial cells were stimulated with tumor necrosis factor-alpha, which resulted in the surface expression of tissue factor. Subsequent exposure to human nonanticoagulated blood at a shear rate of 100 s-1 in a parallel plate perfusion device led to the deposition of polymerized fibrin, which covered 63% of the endothelial surface. In addition, numerous platelet aggregates (71 per 10 mm cross- section) and leukocytes (53 +/- 6/mm2) were deposited on stimulated endothelial cells, whereas no fibrin and only a few platelet aggregates (4 +/- 1 per 10 mm cross-section) and leukocytes (6 +/- 1/mm2) were detected on control cells. A significant portion of the adherent leukocytes bound to fibrin and platelets. However, when the deposition of fibrin and platelet aggregates was inhibited with the anti-tissue factor antibody HTFI-7B8 by 100% and 86%, respectively, leukocyte adherence remained unchanged (68 +/- 6/mm2). This indicated that leukocytes could efficiently adhere to endothelial cells through direct cell-cell contact independent of both thrombin and deposited fibrin. Moreover, this direct adhesion of leukocytes to the endothelial surface was reduced twofold to threefold when fibrin deposition occurred. These data suggest a relationship between endothelial procoagulant and proadhesive properties in that tissue factor-initiated coagulation may contribute to leukocyte adhesion through the formation of an adhesive fibrin/platelet meshwork but concurrently prevents the adhesive endothelial surface to bind leukocytes at its full capacity.

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Deficient iNOS in inflammatory bowel disease intestinal microvascular endothelial cells results in increased leukocyte adhesion

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(00)00391-9 ◽

2000 ◽

Vol 29 (9) ◽

pp. 881-888 ◽

Cited By ~ 38

Author(s):

David G Binion ◽

Parvaneh Rafiee ◽

Kalathur S Ramanujam ◽

Sidong Fu ◽

Pamela J Fisher ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Endothelial Cells ◽

Bowel Disease ◽

Leukocyte Adhesion ◽

Microvascular Endothelial Cells ◽

Inflammatory Bowel ◽

Microvascular Endothelial

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Microfluidic Assay for the Assessment of Leukocyte Adhesion to Human Induced Pluripotent Stem Cell-derived Endothelial Cells (hiPSC-ECs)

Journal of Visualized Experiments ◽

10.3791/58678 ◽

2018 ◽

Cited By ~ 1

Author(s):

Oleh V. Halaidych ◽

Francijna van den Hil ◽

Christine L. Mummery ◽

Valeria V. Orlova

Keyword(s):

Endothelial Cells ◽

Stem Cell ◽

Pluripotent Stem Cell ◽

Leukocyte Adhesion ◽

Induced Pluripotent Stem Cell ◽

Induced Pluripotent

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TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19113428 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3428 ◽

Cited By ~ 14

Author(s):

Hyun-Jung Choi ◽

Na-Eun Kim ◽

Byeong Kim ◽

Miran Seo ◽

Ji Heo

Keyword(s):

Endothelial Cells ◽

Rho Gtpases ◽

Leukocyte Adhesion ◽

Hippo Pathway ◽

Specific Inhibitor ◽

Vascular Diseases ◽

Adhesive Properties ◽

Sprouting Angiogenesis ◽

Tnf Α

YAP/TAZ, a transcriptional co-activator of Hippo pathway, has emerged as a central player in vessel homeostasis such as sprouting angiogenesis and vascular barrier stabilization, during development. However, the role of YAP/TAZ in pathological angiogenesis remains unclear. Here, we demonstrated that YAP/TAZ is a critical mediator in leukocyte-endothelial adhesion induced by the vascular inflammatory cytokine TNF-α. YAP/TAZ was dephosphorylated, translocated from the cytosol to the nucleus, and activated by TNF-α in endothelial cells. A specific inhibitor of Rho GTPases suppressed the TNF-α-induced dephosphorylation of YAP. Knockdown of YAP/TAZ using siRNA significantly reduced the expression of the leukocyte adhesion molecule VCAM1 induced by TNF-α. The adhesion of monocytes to endothelial cells was also markedly reduced by YAP/TAZ silencing. However, knockdown of YAP/TAZ did not affect TNF-α-induced NF-κB signaling. Overall, these results suggest that YAP/TAZ plays critical roles in regulating TNF-α-induced endothelial cell adhesive properties without affecting the NF-κB pathway, and implicate YAP/TAZ as a potential therapeutic target for treating inflammatory vascular diseases.

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LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds

Blood ◽

10.1182/blood-2003-07-2499 ◽

2004 ◽

Vol 103 (3) ◽

pp. 1033-1036 ◽

Cited By ~ 84

Author(s):

Tatsuo Kinashi ◽

Memet Aker ◽

Maya Sokolovsky-Eisenberg ◽

Valentin Grabovsky ◽

Chisato Tanaka ◽

...

Keyword(s):

Shear Flow ◽

Ligand Binding ◽

Phorbol Esters ◽

Leukocyte Adhesion ◽

Deficiency Syndrome ◽

Small Gtpase ◽

High Avidity ◽

Integrin Activation ◽

Leukocyte Adhesion Deficiency ◽

Rap1 Activation

AbstractRecently, we reported a rare leukocyte adhesion deficiency (LAD) associated with severe defects in integrin activation by chemokine signals, despite normal ligand binding of leukocyte integrins.1 We now report that the small GTPase, Rap1, a key regulator of inside-out integrin activation is abnormally regulated in LAD Epstein-Barr virus (EBV) lymphocyte cells. Both constitutive and chemokine-triggered activation of Rap1 were abolished in LAD lymphocytes despite normal chemokine signaling. Nevertheless, Rap1 expression and activation by phorbol esters were intact, ruling out an LAD defect in Rap1 guanosine triphosphate (GTP) loading. The very late antigen 4 (VLA-4) integrin abnormally tethered LAD EBV lymphocytes to its ligand vascular cell adhesion molecule 1 (VCAM-1) under shear flow due to impaired generation of high-avidity contacts despite normal ligand binding and intact avidity to surface-bound anti-VLA-4 monoclonal antibody (mAb). Thus, a defect in constitutive Rap1 activation results in an inability of ligand-occupied integrins to generate high-avidity binding to ligand under shear flow. This is a first report of an inherited Rap1 activation defect associated with a pathologic disorder in leukocyte integrin function, we herein term it “LAD-III.” (Blood. 2004;103:1033-1036)

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