Coordinated and unique functions of the E-selectin ligand ESL-1 during inflammatory and hematopoietic recruitment in mice

Sreeramkumar, Vinatha; Leiva, Magdalena; Stadtmann, Anika; Pitaval, Christophe; Ortega-Rodríguez, Inés; Wild, Martin K.; Lee, Brendan; Zarbock, Alexander; Hidalgo, Andrés

doi:10.1182/blood-2013-07-514497

Cited by 30 publications

(25 citation statements)

References 33 publications

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“…Although we identified PSGL-1 as the dominant functional P-selectin ligand on Tregs, consistent with observations in other leukocyte subsets (55,56), identifying the functional E-selectin ligands on Tregs is likely to be more challenging. Several leukocyte-expressed E-selectin ligands, including PSGL-1, E-selectin ligand-1, CD44, and CD43, have been identified (9,30,(56)(57)(58). Expression of E-selectin ligand-1 has not been reported on lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T Cells Dynamically Regulate Selectin Ligand Function during Multiple Challenge Contact Hypersensitivity

Abeynaike

Deane

Westhorpe

et al. 2014

The Journal of Immunology

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Regulatory T cells (Tregs) play critical roles in restricting T cell–mediated inflammation. In the skin, this is dependent on expression of selectin ligands required for leukocyte rolling in dermal microvessels. However, whether there are differences in the molecules used by Tregs and proinflammatory T cells to undergo rolling in the skin remains unclear. In this study, we used spinning disk confocal microscopy in Foxp3-GFP mice to visualize rolling of endogenous Tregs in dermal postcapillary venules. Tregs underwent consistent but low-frequency rolling interactions under resting and inflamed conditions. At the early stage of the response, Treg adhesion was minimal. However, at the peak of inflammation, Tregs made up 40% of the adherent CD4+ T cell population. In a multiple challenge model of contact hypersensitivity, rolling of Tregs and conventional CD4+ T cells was mostly dependent on overlapping contributions of P- and E-selectin. However, after a second challenge, rolling of Tregs but not conventional CD4+ T cells became P-selectin independent, and Tregs showed reduced capacity to bind P-selectin. Moreover, inhibition of E-selectin at this time point resulted in exacerbation of inflammation. These findings demonstrate that in this multiple challenge model of inflammation, Treg selectin binding capacity and the molecular basis of Treg rolling can be regulated dynamically.

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Section: Discussionmentioning

confidence: 99%

Regulatory T Cells Dynamically Regulate Selectin Ligand Function during Multiple Challenge Contact Hypersensitivity

Abeynaike

Deane

Westhorpe

et al. 2014

The Journal of Immunology

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“…The PNEE acts in a manner similar to Yi-Qi-Fu-Sheng, a Chinese herbal formula, and Ganoderma lucidum, a traditional Chinese medicinal mushroom; all of these agents exhibit a concentration-dependent inhibitory effect on HCT-116 cell invasion and migration by decreasing wound healing ability and MMP-2 and/or MMP-9 activity (Chen et al, 2010;Deng et al, 2013). With the exception of the regulation of cell-cell interactions in the surrounding ECM and stromal substrate through decreases in MMP expression, the regulation of the permeability of cell-cell contact junctions and of the expression of junction proteins constitutes an important mechanism for suppressing migration and decreasing the invasion potential (Barthel et al, 2013;Sreeramkumar et al, 2013). In cell-cell contact structures, gap junctions, tight junctions, adherens junctions and desmosomes are distinct major intercellular structures that allow communication between neighboring cells and that maintain the integrity of the monolayer (Martínez-Palomo, 1970).…”

Section: Discussionmentioning

confidence: 99%

Effects ofPanax notoginsengon the Metastasis of Human Colorectal Cancer Cells

Hsieh

Kuo

et al. 2016

Am. J. Chin. Med.

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The goal of this study was to investigate the effect of the Panax notoginseng ethanol extract (PNEE) on the regulation of human colorectal cancer (CRC) metastasis. The migratory, invasive, and adhesive abilities and the expression of metastasis-associated regulatory molecules in cultured human CRC cells (HCT-116) treated with the PNEE were analyzed in this study. The migratory and invasive abilities of HCT-116 cells were reduced after PNEE treatment. The incubation of HCT-116 cells with the PNEE for 24 h decreased MMP-9 expression and increased E-cadherin expression compared with the control group. The adhesion reaction assay indicated that treatment with the PNEE led to significantly decreased HCT-116 adhesion to endothelial cells (EA.hy926 cells). The integrin-1 protein levels in HCT-116 cells were significantly decreased following treatment with the PNEE. Similarly, the protein levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were significantly decreased by treatment of the EA.hy926 endothelial cells with PNEE. A scanning electron microscope (SEM) examination indicated that HCT-116 cells treated with LPS combined with the PNEE had a less flattened and retracted shape compared with LPS-treated cells, and this change in shape was found to be a phenomenon of extravasation invasion. The transepithelial electrical resistance (TEER) of the EA.hy926 endothelial cell monolayer increased after incubation with the PNEE for 24 h. A cell-cell permeability assay indicated that HCT-116 cells treated with the PNEE displayed significantly reduced levels of phosphorylated VE-cadherin (p-VE-cadherin). These results demonstrate the antimetastatic properties of the PNEE and show that the PNEE affects cells by inhibiting cell migration, invasion, and adhesion and regulating the expression of metastasis-associated signaling molecules.

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“…Indeed, ICAM-1 can enhance immune cell adhesion and migration (49). These integrins mediate strong adhesion between cancer cells and endothelial cells (50), and this process promotes the transmigration of cancer cells through the endothelium to metastatic sites (51,52). Our previous study showed that P. notoginseng exerts anti-metastasis effects in HCT-116 cells by decreasing adhesion activity through reduction in the levels of such adhesion molecules, including integrin-1, E-selectin and ICAM-1 (9).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of human colorectal cancer metastasis by notoginsenoside R1, an important compound from Panax notoginseng

Lee

Hsieh

et al. 2016

Oncology Reports

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Abstract. Panax notoginseng (P. notoginseng) and its components are used as traditional Chinese medicine for cardiovascular disease, although studies concerning the anti-metastatic properties of these compounds are limited. The goal of this study was to investigate the effects of notoginsenoside R1 (NGR1), an important compound derived from P. notoginseng, on the metastasis of human colorectal cancer (CRC). The migratory, invasive, and adhesive abilities of cultured human CRC cells (HCT-116) treated with NGR1 and expression of metastasis-associated regulatory molecules were assessed. The migratory and invasive abilities of the HCT-116 cells were reduced after treatment with 75, 150 or 300 µM NGR1 for 24 h. When HCT-116 cells were incubated with 150 or 300 µM NGR1 for 24 h, matrix metalloproteinase (MMP)-9 expression was reduced compared with that of the control group. In the adhesion reaction assays, treatment with 150 or 300 µM NGR1 led to significantly decreased adhesion of the HCT-116 cells to endothelial cells (EA.hy926 cells). Levels of integrin-1 protein were significantly decreased in the HCT-116 cells following treatment with 75, 150 or 300 µM NGR1, and levels of E-selectin and intercellular adhesion molecule 1 (ICAM-1) proteins were significantly decreased in the EA.hy926 cells treated with 75, 150 or 300 µM NGR1. Scanning electron microscopy examination indicated that HCT-116 cells treated with lipopolysaccharide (LPS) combined with 300 µM NGR1 exhibited a less flattened and retracted shape compared with cells treated with LPS alone, and this change in shape is characteristic of extravasation. Additionally, the transepithelial electrical resistance of the EA.hy926 endothelial cell monolayer increased after incubation with 150 or 300 µM NGR1 for 24 h. Overall, these results demonstrated the anti-metastatic properties of 150 or 300 µM NGR1, a compound that affects CRC metastasis by inhibiting cell migration, invasion, and adhesion and by regulating expression of metastasis-associated signalling molecules.

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Coordinated and unique functions of the E-selectin ligand ESL-1 during inflammatory and hematopoietic recruitment in mice

Cited by 30 publications

References 33 publications

Regulatory T Cells Dynamically Regulate Selectin Ligand Function during Multiple Challenge Contact Hypersensitivity

Regulatory T Cells Dynamically Regulate Selectin Ligand Function during Multiple Challenge Contact Hypersensitivity

Effects ofPanax notoginsengon the Metastasis of Human Colorectal Cancer Cells

Inhibition of human colorectal cancer metastasis by notoginsenoside R1, an important compound from Panax notoginseng

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