scholarly journals Endothelial-dependent Mechanisms Regulate Leukocyte Transmigration: A Process Involving the Proteasome and Disruption of the Vascular Endothelial–Cadherin Complex at Endothelial Cell-to-Cell Junctions

1997 ◽  
Vol 186 (4) ◽  
pp. 517-527 ◽  
Author(s):  
Jennifer R. Allport ◽  
Han Ding ◽  
Tucker Collins ◽  
Mary E. Gerritsen ◽  
Francis W. Luscinskas
Keyword(s):  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Cell Junctions ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Vascular Endothelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Leukocyte Transmigration

Although several adhesion molecules expressed on leukocytes (β1 and β2 integrins, platelet endothelial cell adhesion molecule 1 [PECAM-1], and CD47) and on endothelium (intercellular adhesion molecule 1, PECAM-1) have been implicated in leukocyte transendothelial migration, less is known about the role of endothelial lateral junctions during this process. We have shown previously (Read, M.A., A.S. Neish, F.W. Luscinskas, V.J. Palambella, T. Maniatis, and T. Collins. 1995. Immunity. 2:493–506) that inhibitors of the proteasome reduce lymphocyte and neutrophil adhesion and transmigration across TNF-α–activated human umbilical vein endothelial cell (EC) monolayers in an in vitro flow model. The current study examined EC lateral junction proteins, principally the vascular endothelial (VE)–cadherin complex and the effects of proteasome inhibitors (MG132 and lactacystin) on lateral junctions during leukocyte adhesion, to gain a better understanding of the role of EC junctions in leukocyte transmigration. Both biochemical and indirect immunofluorescence analyses of the adherens junction zone of EC monolayers revealed that neutrophil adhesion, not transmigration, induced disruption of the VE–cadherin complex and loss of its lateral junction localization. In contrast, PECAM-1, which is located at lateral junctions and is implicated in neutrophil transmigration, was not altered. These findings identify new and interrelated endothelial-dependent mechanisms for leukocyte transmigration that involve alterations in lateral junction structure and a proteasome-dependent event(s).

scholarly journals Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells.

1988 ◽  
Vol 107 (1) ◽  
pp. 321-331 ◽  
Author(s):  
M L Dustin ◽  
T A Springer
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Peripheral Blood Lymphocytes ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Lymphocyte Adhesion

Intercellular adhesion molecule-1 (ICAM-1) on the surface of cultured umbilical vein and saphenous vein endothelial cells was upregulated between 2.5- and 40-fold by rIL-1, rTNF, LPS and rIFN gamma corresponding to up to 5 X 10(6) sites/cell. Endothelial cell ICAM-1 was a single band of 90 kD in SDS-PAGE. Purified endothelial cell ICAM-1 reconstituted into liposomes and bound to plastic was an excellent substrate for both JY B lymphoblastoid cell and T lymphoblast adhesion. Adhesion to endothelial cell ICAM-1 in planar membranes was blocked completely by monoclonal antibodies to lymphocyte function associated antigen-1 (LFA-1) or ICAM-1. Adhesion to artificial membranes was most sensitive to ICAM-1 density within the physiological range found on resting and stimulated endothelial cells. Adhesion of JY B lymphoblastoid cells, normal and genetically LFA-1 deficient T lymphoblasts and resting peripheral blood lymphocytes to endothelial cell monolayers was also assayed. In summary, LFA-1 dependent (60-90% of total adhesion) and LFA-1-independent basal adhesion was observed and the use of both adhesion pathways by different interacting cell pairs was increased by monokine or lipopolysaccharide stimulation of endothelial cells. The LFA-1-dependent adhesion could be further subdivided into an LFA-1/ICAM-1-dependent component which was increased by cytokines and a basal LFA-1-dependent, ICAM-1-independent component which did not appear to be affected by cytokines. We conclude that ICAM-1 is a regulated ligand for lymphocyte-endothelial cell adhesion, but at least two other major adhesion pathways exist.

scholarly journals ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-α-activated vascular endothelium under flow

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 584-592 ◽  
Author(s):  
Lin Yang ◽  
Richard M. Froio ◽  
Tracey E. Sciuto ◽  
Ann M. Dvorak ◽  
Ronen Alon ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelium ◽  
Fluorescent Protein ◽  
Umbilical Vein ◽  
Cytoplasmic Tail ◽  
Cell Junctions ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α

Abstract In vivo, leukocyte transendothelial migration (TEM) occurs at endothelial cell junctions (paracellular) and nonjunctional (transcellular) locations, whereas in vitro models report that TEM is mostly paracellular. The mechanisms that control the route of leukocyte TEM remain unknown. Here we tested the hypothesis that elevated intercellular adhesion molecule-1 (ICAM-1) expression regulates the location of polymorphonuclear leukocyte (PMN) TEM. We used an in vitro flow model of tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelium cells (HUVECs) or an HUVEC cell line transfected with ICAM-1GFP (green fluorescent protein) and live-cell fluorescence microscopy to quantify the location of PMN adhesion and TEM. We observed robust transcellular TEM with TNF-α-activated HUVECs and ICAM-1GFP immortalized HUVECS (iHUVECs). In contrast, primary CD3+ T lymphocytes exclusively used a paracellular route. Endothelial ICAM-1 was identified as essential for both paracellular and transcellular PMN transmigration, and interfering with ICAM-1 cytoplasmic tail function preferentially reduced transcellular TEM. We also found that ICAM-1 surface density and distribution as well as endothelial cell shape contributed to transcellular TEM. In summary, ICAM-1 promotes junctional and nonjunctional TEM across inflamed vascular endothelium via distinct cytoplasmic tail associations. (Blood. 2005;106:584-592)

Anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells

1992 ◽  
Vol 262 (6) ◽  
pp. H1891-H1898 ◽  
Author(s):  
N. Yoshida ◽  
D. N. Granger ◽  
D. C. Anderson ◽  
R. Rothlein ◽  
C. Lane ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Receptor Antagonist ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Leukotriene B4 ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Lipoxygenase Inhibitor ◽  
Neutrophil Adherence

Previous studies have shown enhanced neutrophil adhesion to endothelial cells exposed to anoxia and then reoxygenated (A/R). To define the molecular basis for these observations, we evaluated the relative roles of CD11/CD18 determinants (CD11a and CD11b) of neurtrophils and the endothelial adhesion proteins intercellular adhesion molecule 1 (ICAM-1) and endothelial-leukocyte adhesion molecule 1 (ELAM-1). Human umbilical vein endothelial cell (HUVEC) monolayers were exposed to anoxia for 30 min, reoxygenated, and then reacted with 51Cr-labeled neutrophils in adhesion assays. Neutrophil adhesion to HUVEC exposed to A/R was significantly increased (2.7-fold) as compared with that observed with normoxic (control) HUVEC. This A/R-induced hyperadherence was significantly diminished by monoclonal antibodies (MAb) directed at CD11a, CD11b, CD18 or ICAM-1, but not by MAb directed at ELAM-1. The inhibitory effects of anti-CD11a and anti-CD11b were additive and equivalent to that of anti-CD18 MAb. A/R did not elicit increased levels of ICAM-1 or ELAM-1 mRNA or surface protein. However, immunofluorescence flow cytometry indicated that incubation of neutrophils in supernatants of A/R-conditioned HUVEC elicited an increase of surface CD11b and CD18, but not CD11a. Supernatants from A/R-conditioned HUVEC promoted neutrophil adherence to naive HUVEC, and this hyperadhesivity was diminished by a platelet-activating factor (PAF) receptor antagonist and catalase but not by a 5-lipoxygenase inhibitor, a leukotriene B4 receptor antagonist, or superoxide dismutase. These studies indicate that A/R promotes neutrophil adherence via CD11a/CD18- and CD11b/CD18-dependent interactions with ICAM-1 that appear to be mediated by hydrogen peroxide and PAF.

Systemic Endothelial Cell Markers in Primary Antiphospholipid Syndrome

2000 ◽  
Vol 84 (11) ◽  
pp. 742-746 ◽  
Author(s):  
Frances M. Williams ◽  
Kiran Parmar ◽  
Graham R. Hughes ◽  
Beverley Hunt
Keyword(s):  
Endothelial Cell ◽  
Tissue Factor ◽  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Primary Antiphospholipid Syndrome ◽  
Cell Of Origin ◽  
Intercellular Adhesion Molecule 1

SummaryThe pathogenic mechanism underlying the prothrombotic tendency of Hughes’ or antiphospholipid syndrome (APS) has not been elucidated. Numerous procoagulant mechanisms have been tested including platelet activation, monocyte tissue factor (TF) expression and endothelial cell (EC) activation. There is some evidence for the latter from studies on cultured human umbilical vein endothelial cells (HUVEC). Incubation with antiphospholipid antibodies (aPL) induces EC activation in vitro. We investigated whether there was evidence of EC perturbation in vivo using enzyme-linked immunosorbant assays (ELISAs) for soluble markers of EC dysfunction. Serum and plasma were collected from controls and patients with primary APS and ELISAs performed to quantify soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), endothelin-1 (ET-1), von Willebrand factor (vWF) and soluble tissue factor (sTF). In addition, soluble p-selectin (p-selectin) and vascular endothelial growth factor (VEGF) were measured: the former as a marker of platelet activation, the latter as a potential mediator of TF expression. No significant differences in the levels of blood-borne soluble markers were detected between the patient and control groups except for VEGF and sTF, patients having significantly higher levels of VEGF and sTF than controls (p <0.05). These results suggest plasma soluble tissue factor and VEGF may play a role in the pathogenesis of thrombosis in APS, although the cell of origin of these molecules remains unclear.

scholarly journals Synthetic Colloids Attenuate Leukocyte-Endothelial Interactions by Inhibition of Integrin Function

2005 ◽  
Vol 103 (4) ◽  
pp. 759-767 ◽  
Author(s):  
Boris Nohé ◽  
Tanja Johannes ◽  
Jörg Reutershan ◽  
Albert Rothmund ◽  
Helene A. Haeberle ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Tissue Injury ◽  
Severe Infection ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Cell Activation

Background It has been suspected that synthetic colloids may interfere with leukocyte adhesion by down-regulation of endothelial cell adhesion molecules. Although inhibition of endothelial inflammation might reduce leukocyte-related tissue injury, the same mechanism may be detrimental for host defense during severe infection. Regarding the widespread use of colloids, the authors performed a laboratory investigation to determine the mechanisms by which synthetic colloids interfere with leukocyte-endothelial interactions. Methods Adhesion molecule expression on native and cytokine-activated endothelium from umbilical veins was measured after pretreatment with gelatin and various preparations of dextran or hydroxyethyl starch. Inhibition of neutrophil adhesion to activated endothelium was examined in a flow chamber by perfusion of untreated and colloid-treated neutrophils over colloid-pretreated endothelium at 2 dyn/cm. Comparisons were made between untreated controls, colloid-pretreated endothelium, and colloid-cotreated neutrophils. Results Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and P-selectin were not attenuated by any colloid. Accordingly, colloid pretreatment of endothelium alone did not reduce neutrophil adhesion. In contrast, when neutrophils were cotreated by addition of colloids to the perfusate immediately before perfusion, adhesion decreased by 31-51% (P &lt; 0.05) regardless of the colloid type. As indicated by the twofold increased rolling fractions, this reduction was due to an inhibition of neutrophil integrins. Conclusions This study shows that synthetic colloids inhibit neutrophil adhesion by a neutrophil-dependent mechanism rather than interfering with endothelial cell activation. This suggests that inhibition of leukocyte sequestration by volume support is a common and transient phenomenon depending on the colloid concentration in plasma.

scholarly journals Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules.

1991 ◽  
Vol 173 (6) ◽  
pp. 1553-1557 ◽  
Author(s):  
B S Bochner ◽  
F W Luscinskas ◽  
M A Gimbrone ◽  
W Newman ◽  
S A Sterbinsky ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Cell Type ◽  
Human Basophils

Cytokines such as interleukin 1 (IL-1) promote adhesiveness in human umbilical vein endothelial cells for leukocytes including basophils, eosinophils, and neutrophils, and induce expression of adherence molecules including ICAM-1 (intercellular adhesion molecule-1), ELAM-1 (endothelial-leukocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1). In the present study, blocking monoclonal antibodies (mAb) recognizing ICAM-1, ELAM-1, and VCAM-1 have been used to compare their roles in IL-1-induced adhesion of human basophils, eosinophils, and neutrophils. IL-1 treatment of endothelial cell monolayers for 4 hours induced a four- to eight-fold increase in adhesion for each cell type. Treatment of endothelial cells with either anti-ICAM-1 or anti-ELAM-1 mAb inhibited IL-1-induced adherence of each cell type. In contrast, treatment with anti-VCAM-1 mAb inhibited basophil and eosinophil (but not neutrophil) adhesion, and was especially effective in blocking eosinophil adhesion. The effects of these mAb were at least additive. Indirect immunofluorescence and flow cytometry demonstrated expression of VLA-4 alpha (very late activation antigen-4 alpha, a counter-receptor for VCAM-1) on eosinophils and basophils but not on neutrophils. These data document distinct roles for ICAM-1, ELAM-1, and VCAM-1 during basophil, eosinophil, and neutrophil adhesion in vitro, and suggest a novel mechanism for the recruitment of eosinophils and basophils to sites of inflammation in vivo.

scholarly journals Endothelial reticulon-4B (Nogo-B) regulates ICAM-1–mediated leukocyte transmigration and acute inflammation

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2284-2295 ◽  
Author(s):  
Annarita Di Lorenzo ◽  
Thomas D. Manes ◽  
Alberto Davalos ◽  
Paulette L. Wright ◽  
William C. Sessa
Keyword(s):  
Bone Marrow ◽  
Endothelial Cell ◽  
Critical Role ◽  
Vascular Endothelial Cell ◽  
Intercellular Adhesion Molecule ◽  
Immune Functions ◽  
Intercellular Adhesion Molecule 1 ◽  
Leukocyte Transmigration

Abstract The reticulon (Rtn) family of proteins are localized primarily to the endoplasmic reticulum (ER) of most cells. The Rtn-4 family, (aka Nogo) consists of 3 splice variants of a common gene called Rtn-4A, Rtn-4B, and Rtn-4C. Recently, we identified the Rtn-4B (Nogo-B) protein in endothelial and smooth muscle cells of the vessel wall, and showed that Nogo-B is a regulator of cell migration in vitro and vascular remodeling and angiogenesis in vivo. However, the role of Nogo-B in inflammation is still largely unknown. In the present study, we use 2 models of inflammation to show that endothelial Nogo-B regulates leukocyte transmigration and intercellular adhesion molecule-1 (ICAM-1)–dependent signaling. Mice lacking Nogo-A/B have a marked reduction in neutrophil and monocyte recruitment to sites of inflammation, while Nogo-A/B−/− mice engrafted with wild-type (WT) bone marrow still exhibit impaired inflammation compared with WT mice engrafted with Nogo-A/B−/− bone marrow, arguing for a critical role of host Nogo in this response. Using human leukocytes and endothelial cells, we show mechanistically that the silencing of Nogo-B with small interfering RNA (siRNA) impairs the transmigration of neutrophils and reduces ICAM-1–stimulated phosphorylation of vascular endothelial-cell cadherin (VE-cadherin). Our results reveal a novel role of endothelial Nogo-B in basic immune functions and provide a key link in the molecular network governing endothelial-cell regulation of diapedesis.

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