scholarly journals EA-1, a novel adhesion molecule involved in the homing of progenitor T lymphocytes to the thymus.

1991 ◽  
Vol 114 (5) ◽  
pp. 1069-1078 ◽  
Author(s):  
B A Imhof ◽  
P Ruiz ◽  
B Hesse ◽  
R Palacios ◽  
D Dunon

The mouse progenitor T lymphocyte (pro-T) cell line FTF1 binds in vitro to thymus blood vessels, the thymic capsule, and liver from newborn mice. A mAb, EA-1, raised against an embryonic mouse endothelial cell line, blocked adhesion. The antibody also interfered with pro-T cell adhesion to a thymus-derived mouse endothelial cell line; it had no effect on the adhesion of mature T lymphocytes and myeloid cells. The antigen recognized by EA-1 is located on the vascular endothelium of various mouse tissues and absent on pro-T cells. EA-1 antibody precipitates molecules with apparent molecular weights of 110,000, 140,000, 160,000, and 200,000. Immunoclearing and binding-inhibition studies with antibodies against known adhesion molecules suggest that the EA-1 antigen is a novel adhesion molecule involved in colonization of the embryonic thymus by T cell progenitors.

1997 ◽  
Vol 11 (13) ◽  
pp. 1187-1197 ◽  
Author(s):  
Arumugam Muruganandam ◽  
Leonie Moorhouse Herx ◽  
Robert Monette ◽  
Jon P. Durkin ◽  
Danica B. Stanimirovic

2012 ◽  
Vol 31 (4) ◽  
pp. 364-371 ◽  
Author(s):  
Tanja Krüger ◽  
Yi Cao ◽  
Søren K. Kjærgaard ◽  
Lisbeth E. Knudsen ◽  
Eva C. Bonefeld-Jørgensen

Phthalates are industrial chemicals used in many cosmetics. We evaluated an in vitro model for eye irritancy testing using the human corneal endothelial cell line B4G12. Cell proliferation and toxicity were assessed after exposing to di- n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP), diisodecyl phthalate (DIDP), di- n-octyl phthalate (DnOP), and di-isononyl phthalate (DINP). Gene expression and secretion of inflammatory cytokines were evaluated after exposure to DBP. Decreased cell proliferation was observed for the phthalates DBP, BBP, and DEHP, and cell toxicity was observed for DBP and BBP. Upon DBP exposure at nontoxic concentrations, a significant increased gene expression and cytokine cell secretion were observed for interleukin-1β (IL-1β) and IL-8, and also an increased IL-6 secretion was observed. In conclusion, the human corneal endothelial cell line B4G12 may be a potential model for inflammatory eye irritancy testing of phthalates.


2017 ◽  
Vol 42 (6) ◽  
pp. 1013-1017 ◽  
Author(s):  
Ramzi Shawahna ◽  
Kayathiri Ganeshamoorthy ◽  
Luo Huilong ◽  
Jean-Michel Scherrmann ◽  
Pierre-Olivier Couraud ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
pp. e000432 ◽  
Author(s):  
Lorena Carmona-Rodríguez ◽  
Diego Martínez-Rey ◽  
Maria Jesús Fernández-Aceñero ◽  
Alicia González-Martín ◽  
Mateo Paz-Cabezas ◽  
...  

BackgroundTumor-infiltrating lymphocytes (TILs), mainly CD8+ cytotoxic T lymphocytes (CTL), are linked to immune-mediated control of human cancers and response to immunotherapy. Tumors have nonetheless developed specific mechanisms that selectively restrict T cell entry into the tumor microenvironment. The extracellular superoxide dismutase (SOD3) is an anti-oxidant enzyme usually downregulated in tumors. We hypothesize that upregulation of SOD3 in the tumor microenvironment might be a mechanism to boost T cell infiltration by normalizing the tumor-associated endothelium.ResultsHere we show that SOD3 overexpression in endothelial cells increased in vitro transmigration of naïve and activated CD4+ and CD8+ T cells, but not of myeloid cells. Perivascular expression of SOD3 also specifically increased CD4+ and CD8+ effector T cell infiltration into tumors and improved the effectiveness of adoptively transferred tumor-specific CD8+ T cells. SOD3-induced enhanced transmigration in vitro and tumor infiltration in vivo were not associated to upregulation of T cell chemokines such as CXCL9 or CXCL10, nor to changes in the levels of endothelial adhesion receptors such as intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1). Instead, SOD3 enhanced T cell infiltration via HIF-2α-dependent induction of specific WNT ligands in endothelial cells; this led to WNT signaling pathway activation in the endothelium, FOXM1 stabilization, and transcriptional induction of laminin-α4 (LAMA4), an endothelial basement membrane component permissive for T cell infiltration. In patients with stage II colorectal cancer, SOD3 was associated with increased CD8+ TIL density and disease-free survival. SOD3 expression was also linked to a T cell–inflamed gene signature using the COAD cohort from The Cancer Genome Atlas program.ConclusionOur findings suggest that SOD3-induced upregulation of LAMA4 in endothelial cells boosts selective tumor infiltration by T lymphocytes, thus transforming immunologically “cold” into “hot” tumors. High SOD3 levels are associated with human colon cancer infiltration by CD8+ T cells, with potential consequences for the clinical outcome of these patients. Our results also uncover a cell type–specific, distinct activity of the WNT pathway for the regulation of T cell infiltration into tumors.


2005 ◽  
Vol 289 (2) ◽  
pp. H542-H548 ◽  
Author(s):  
Ramzi Ockaili ◽  
Ramesh Natarajan ◽  
Fadi Salloum ◽  
Bernard J. Fisher ◽  
Drew Jones ◽  
...  

The CXC chemokine IL-8, which promotes adhesion, activation, and transmigration of polymorphonuclear neutrophils (PMN), has been associated with production of tissue injury in reperfused myocardium. Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric peptide that is a key regulator of genes such as heme oxygenase (HO)-1 expressed under hypoxic conditions. We hypothesized that HO-1 plays an important role in regulating proinflammatory mediator production under conditions of ischemia-reperfusion. HIF-1 was activated in the human microvascular endothelial cell line (HMEC-1) with the prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG). DMOG significantly attenuated cytokine-induced IL-8 promoter activity and protein secretion and cytokine-induced PMN migration across human microvascular endothelial cell line HMEC-1 monolayers. In vivo studies in a rabbit model of myocardial ischemia-reperfusion showed that rabbits pretreated with a 20 mg/kg DMOG infusion ( n = 6) 24 h before study exhibited a 21.58 ± 1.76% infarct size compared with 35.25 ± 2.06% in saline-treated ischemia-reperfusion animals ( n = 6, change in reduction = 39%; P < 0.001). In DMOG-pretreated (20 mg/kg) animals, plasma IL-8 levels at 3 h after onset of reperfusion were 405 ± 40 pg/ml vs. 790 ± 40 pg/ml in saline-treated ischemia-reperfusion animals ( P < 0.001). DMOG pretreatment reduced myocardial myeloperoxidase activity, expressed as number of PMN per gram of myocardium, to 1.43 ± 0.59 vs. 4.86 ± 1.1 ( P = 0.012) in saline-treated ischemia-reperfused hearts. Both in vitro and in vivo DMOG-attenuated IL-8 production was associated with robust HO-1 expression. Thus our data show that HIF-1 activation induces substantial HO-1 expression that is associated with attenuated proinflammatory chemokine production by microvascular endothelium in vitro and in vivo.


2008 ◽  
Vol 63 (11-12) ◽  
pp. 813-820 ◽  
Author(s):  
İhsan Çalış ◽  
Matej Barbič ◽  
Guido Jürgenliemk

Abstract Together with two known cycloartane-type glycosides, askendosides D (3-O-[α-arabinopyranosyl-( 1→2)-β-xylopyranosyl]-6-O-β-xylopyranosyl-cycloastragenol, 2) and G (3-O- [α-arabinopyranosyl-(1→2)-β-xylopyranosyl]-16-O-β-glucopyranosyl-3β,6α,16β,24(R),25- pentahydroxycycloartane, 3), also a new monodesmosidic cycloartane-type glycoside, elongatoside (1), was isolated from the roots of Astragalus elongatus and identified as 3-O- [α-arabinopyranosyl-(1→2)-β-xylopyranosyl]-cycloastragenol. All structures were unambiguously determined by means of spectroscopic and spectrometric methods (1D and 2D NMR, ESI-MS). The isolated compounds were tested for the inhibition of proliferation and ICAM-1 expression in vitro using the human microvascular endothelial cell line (HMEC-1). 1 showed weak activity in the ICAM-1 assay.


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