scholarly journals Five tumor necrosis factor-inducible cell adhesion mechanisms on the surface of mouse endothelioma cells mediate the binding of leukocytes.

1993 ◽  
Vol 121 (3) ◽  
pp. 655-664 ◽  
Author(s):  
M Hahne ◽  
U Jäger ◽  
S Isenmann ◽  
R Hallmann ◽  
D Vestweber
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Cell Line ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Tnf Alpha ◽  
The Novel ◽  
Adhesion Mechanism ◽  
Tnf Induction ◽  
Necrosis Factor

We have distinguished five TNF-alpha-inducible cell adhesion mechanisms on microvasculature-derived endothelioma cells of the mouse which mediate the binding of different types of leukocytes. Three of these mechanisms could be identified as the mouse homologs of ICAM-1, VCAM-1, and E-selectin, of which the latter was defined by the novel mAb 21KC10. The fourth TNF-alpha-inducible cell adhesion mechanism was blocked by antibodies specific for mouse P-selectin. We have recently shown that TNF-alpha stimulates the synthesis of P-selectin in mouse endothelioma cells (A. Weller, S. Isenmann, D. Vestweber. 1992. J. Biol. Chem. 267:15176-15183). Here we show that this stimulation leads to maximal cell surface expression levels within 4 h after stimulation while the same endothelioma cells are also able to upregulate P-selectin at the cell surface within minutes after stimulation with PMA. Both effects are additive. The fifth TNF-induced cell adhesion mechanism is defined by mediating the binding to the mouse monocyte/macrophage cell line J774. This adhesion mechanism is not inhibited by antibodies against any of the other four CAMs; it functions well at 7 degrees C (in contrast to ICAM-1 and VCAM-1) and it is as active after 16 h of TNF induction as after 4 h (in contrast to E- and P-selectin). Furthermore, this new adhesion mechanism only functions on two of three endothelioma cell lines and is undetectable on the third, although ICAM-1, VCAM-1, E-selectin, and P-selectin could be demonstrated to function well on this cell line. Thus, in addition to the three known TNF-inducible CAMs, ICAM-1, VCAM-1, and E-selectin, also P-selectin and a fifth, as yet molecularly undefined cell adhesion mechanism, are TNF inducible at the cell surface of mouse endothelioma cells.

A Cell-Based Adhesion Molecule Bioassay Detects Unexpected Properties of Plasma From Patients with Sickle Cell Disease with Documented Pulmonary Hypertension

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2120-2120
Author(s):  
Antje Ask ◽  
Laurel G. Mendelsohn ◽  
Shoaib Alam ◽  
Alem Mehari ◽  
Caterina Minniti ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Heart Catheterization ◽  
Soluble Adhesion Molecules

Abstract Abstract 2120 Pulmonary hypertension (PH) is a common complication in adults with sickle cell disease (SCD) associated with early mortality. Several mechanistic pathways appear to be involved in PH in SCD, one of them being activation of pulmonary endothelium and increased adherence of circulation blood cells. In the past, levels of soluble adhesion molecules in the plasma of patients with SCD have been found to correlate with severity of pulmonary hypertension and risk of mortality. We investigated the association between endothelial-cell based adhesion molecules and markers of PH. We developed a new cell-based ELISA assay and evaluated the induction of cell surface expression of adhesion molecules on cultured microvascular endothelium cells by plasma from subjects with SCD who had undergone right heart catheterization. We found no difference in baseline Intercellular Cell Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1) and P-selectin induction by SCD plasma compared to healthy controls. Surprisingly, we found an inverse relationship of cell surface VCAM-1 induction with diagnosis and severity of PH, as indicated by mean pulmonary artery pressure (mPAP) on right heart catheterization. Patients who fell into the upper quartile of VCAM-1 induction had mPAP of 27.6 ± 3.2 mmHg, compared to the middle two quartiles 32 ± 2.3 mmHg, and lower quartile 38.2 ± 4.0 mmHg, (p=0.034). The prevalence of abnormally high pulmonary vascular resistance (>2 standard deviations above the mean) in the high, medium or low VCAM-1 induction groups was 20%, 35% and 80%, respectively (p=0.0066). We also found statistically significant correlations of cell surface VCAM-1 to cardiac output, transpulmonary gradient, pulse pressure, Doppler echocardiography tricuspid regurgitation velocity (TRV) and a marker of systemic iron overload, serum ferritin. Induced cell surface VCAM-1 expression did not correlate significantly in the same subjects with the plasma level of soluble VCAM-1, a previously documented marker associated with high TRV. We found very similar patterns of induction of cell surface expression of P-selectin. These results indicate that the ability of plasma to induce cell surface expression of cell adhesion molecules is a new marker predictive of the diagnosis of catheterization-proven PH in SCD, but it is independent of the levels of the soluble ectodomains of these cell adhesion molecules. These results are consistent with recent publications in the cell adhesion molecule field indicating that independent inflammation-mediated mechanisms regulate adhesion molecule expression and its ectodomain shedding via sheddases. Our findings lead us to speculate that increased sheddase activity may contribute to the high levels of soluble adhesion molecules found in PH, simultaneously reducing the level of cell surface adhesion molecules. Future studies of sheddase activity in SCD PH would help to elucidate this interesting observation. Disclosures: No relevant conflicts of interest to declare.

Metalloproteinases Are Involved in Lipopolysaccharide– and Tumor Necrosis Factor-–Mediated Regulation of CXCR1 and CXCR2 Chemokine Receptor Expression

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2173-2185 ◽  
Author(s):  
Masud H. Khandaker ◽  
Gordon Mitchell ◽  
Luoling Xu ◽  
Joseph D. Andrews ◽  
Rajkumari Singh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Proteinase Inhibitors ◽  
Surface Expression ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Metalloproteinase Inhibitors ◽  
Necrosis Factor

The neutrophil-specific G-protein–coupled chemokine receptors, CXCR1 and CXCR2, bind with high affinity to the potent chemoattractant interleukin-8 (IL-8). The mechanisms of IL-8 receptor regulation are not well defined, although previous studies have suggested a process of ligand-promoted internalization as a putative regulatory pathway. Herein, we provide evidence for two distinct processes of CXCR1 and CXCR2 regulation. Confocal microscopy data showed a redistribution of CXCR1 expression from the cell surface of neutrophils to internal compartments after stimulation with IL-8, whereas stimulation with bacterial lipopolysaccharide (LPS) or tumor necrosis factor- (TNF-) did not induce CXCR1 internalization but instead mediated a significant loss of membrane-proximal CXCR1 staining intensity. To investigate whether proteolytic cleavage was the mechanism responsible for LPS- and TNF-–induced downmodulation of IL-8 receptors, we tested a panel of proteinase inhibitors. The downmodulation of CXCR1 and CXCR2 by LPS and TNF- was most dramatically inhibited by metalloproteinase inhibitors; 1,10-phenanthroline and EDTA significantly attenuated LPS- and TNF-–induced loss of CXCR1 and CXCR2 cell surface expression. Metalloproteinase inhibitors also blocked the release of CXCR1 cleavage fragments into the cell supernatants of LPS- and TNF-–stimulated neutrophils. In addition, while treatment of neutrophils with LPS and TNF- inhibited IL-8 receptor–mediated calcium mobilization and IL-8–directed neutrophil chemotaxis, both 1,10-phenanthroline and EDTA blocked these inhibitory processes. In contrast, metalloproteinase inhibitors did not affect IL-8–mediated downmodulation of CXCR1 and CXCR2 cell surface expression or receptor signaling. Thus, these findings may provide further insight into the mechanisms of leukocyte regulation during immunologic and inflammatory responses.

Perfusion with sickle erythrocytes up-regulates ICAM-1 andVCAM-1 gene expression in cultured human endothelial cells

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3232-3241 ◽  
Author(s):  
Yan-Ting Shiu ◽  
Mark M. Udden ◽  
Larry V. McIntire
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Sickle Cell ◽  
Cell Adhesion Molecules ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Human Endothelial Cells ◽  
Sickle Erythrocytes

Sickle cell anemia is characterized by periodic vasoocclusive crises. Increased adhesion of sickle erythrocytes to vascular endothelium is a possible contributing factor to vasoocclusion. This study determined the effect of sickle erythrocyte perfusion at a venous shear stress level (1 dyne/cm2) on endothelial cell (EC) monolayers. Sickle erythrocytes up-regulated intercellular adhesion molecule-1 (ICAM-1) gene expression in cultured human endothelial cells. This was accompanied by increased cell surface expression of ICAM-1 and also elevated release of soluble ICAM-1 molecules. Expression of vascular cell adhesion molecule-1 (VCAM-1) messenger RNA (mRNA) was also strikingly elevated in cultured ECs after exposure to sickle cell perfusion, although increases in membrane-bound and soluble VCAM-1 levels were small. The presence of cytokine interleukin-1β in the perfusion system enhanced the production of ICAM-1 and VCAM-1 mRNA, cell surface expression, and the concentrations of circulating forms. This is the first demonstration that sickle erythrocytes have direct effects on gene regulation in cultured human ECs under well-defined flow environments. The results suggest that perfusion with sickle erythrocytes increases the expression of cell adhesion molecules on ECs and stimulates the release of soluble cell adhesion molecules, which may serve as indicators of injury and/or activation of endothelial cells. The interactions between sickle red blood flow, inflammatory cytokines, and vascular adhesion events may render sickle cell disease patients vulnerable to vasoocclusive crises.

Abnormal tumor necrosis factor receptor I cell surface expression and NF-κB activation in tumor necrosis factor receptor–associated periodic syndrome

2007 ◽  
Vol 58 (1) ◽  
pp. 273-283 ◽  
Author(s):  
Belinda Nedjai ◽  
Graham A. Hitman ◽  
Nasim Yousaf ◽  
Yuti Chernajovsky ◽  
Susanna Stjernberg-Salmela ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Periodic Syndrome ◽  
Necrosis Factor
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