Soluble Forms of Vascular Adhesion Molecules, E‐Selectin, ICAM‐1, and VCAM‐1: Pathological Significance

Gearing, A. J. H.; Hemingway, Ian; Pigoit, Rod; Hughes, Jeremy; Rees, Andrew J.; Cashman, S. J.

doi:10.1111/j.1749-6632.1992.tb51633.x

Cited by 394 publications

(300 citation statements)

References 31 publications

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“…The intraassay variation was found not to exceed lo%, and the interassay variation was 15%. Mean serum levels in normal individuals, as determined by the manufacturers, are 46 ng/ml (range 29-63), 210 ng/ml (range 115-306), and 553 ng/ml (range 395-714) for E-selectin, ICAM-1, and VCAM-1, respectively (17,27). Leukocyte counts for all 73 patients were performed on fresh blood samples collected into tubes containing EDTA.…”

Section: Methodsmentioning

confidence: 99%

Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis

Paleolog

Hunt

Elliott

et al. 1996

Arthritis & Rheumatism

227

117

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Objective. To assess whether monoclonal antibody to tumor necrosis factor a (TNFa) reduces endothelial activation in rheumatoid arthritis (RA).Methods. Levels of serum E-selectin, intercellular adhesion molecule 1 (ICAM-l), and vascular cell adhesion molecule 1 (VCAM-l), and circulating leukocytes (differential counts) were measured in RA patients before and up to 4 weeks after infusion of either placebo or chimeric anti-TNFa antibody cA2 (1 or 10 mg/kg).Results. Treatment with anti-TNFa decreased serum E-selectin and ICAM-1 levels, with the earliest detectable changes observed on days 1-3 after anti-TNFa infusion. No effect on VCAM-1 levels was detected. In parallel, there was a rapid and sustained increase in circulating lymphocytes. The extent of the decrease in serum E-selectin and ICAM-1 levels and the increase in lymphocyte counts was significantly higher (P I 0.05) in patients in whom a clinical benefit of anti-TNFa was observed (120% response, by Paulus criteria, at week 4) compared with that in patients who failed to respond to anti-TNFa at this time point.Conclusion. We propose that decreased serum levels of adhesion molecules may reflect diminished activation of endothelial cells in the synovial microvas-

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Section: Methodsmentioning

confidence: 99%

Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis

Paleolog

Hunt

Elliott

et al. 1996

Arthritis & Rheumatism

227

117

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“…The sICAM-1 level may reflect the expression status of mbICAM-1 on endothelial cells thereby indicating the degree of inflammatory process and/or EC activation. 38 Elevated serum sICAM-1 levels have been noted in various immune and inflammatory disorders including SCA. 39 Indeed, sickle RBCs have been shown to induce mbICAM-1 expression by endothelial cells in culture both in stationary and flow studies.…”

Section: Effect Of Hu On Endothelial Cell Cycle Changesmentioning

confidence: 99%

Hydroxyurea downregulates endothelin-1 gene expression and upregulates ICAM-1 gene expression in cultured human endothelial cells

et al. 2003

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The clinical efficacy of oral hydroxyurea (HU) in adults and children with sickle cell anemia (SCA) cannot solely be explained by its ability to enhance fetal hemoglobin (HbF) expression. Since increased adherence of sickle red blood cells to vascular endothelium is a possible contributing factor to vasoocclusive crisis (VOC), we explored the effect of HU on human endothelial cell (EC) lines (TrHBMEC and EA-hy 926). We demonstrated that HU, in a dose-dependent and reversible manner, significantly decreased (up to threefold) the release of endothelin-1 (ET-1), a vasoconstrictor peptide through downregulation (up to three-fold) of ET-1 gene expression. This finding is of therapeutic relevance as SCA patients exhibit elevated serum levels of ET-1 during episodes of VOC and levels correlate with disease severity. Unexpectedly, HU upregulated (up to three-fold) the expression of membrane-bound intercellular cell adhesion molecule 1 (mbICAM-1) and its soluble form (sICAM-1) with a parallel increase in ICAM-1 mRNA expression. Although ICAM-1 does not appear to be involved in the sickle cell adhesion to vascular endothelium, it may exacerbate vaso-occlusion by promoting leukocyte adhesion. The HU-induced increase in mbICAM-1 may appear inconsistent with the clinical benefits confered by HU. However, both the increase in sICAM-1-and HU-induced leukocyte reduction in patients, may counteract the potentially detrimental effect of elevated mbICAM-1 expression. Also HU reduces the expression of vascular cell adhesion molecule (VCAM-1) on EC. Since HU reduces the very late antigen 4-positive reticulocytes in SCA patients, a ligand for VCAM-1, HU-induced downregulation of VCAM-1 on EC will very likely decrease the reticulocyte-endothelium adhesion. Thus, HU, apart from inducing HbF expression in the red cell, also affects the expression profile of EC compartment.

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“…Of these, ICAM-1 is the best studied with respect to the movement of leukocytes across the endothelium during infection and inflammation where it is known to 'seal' the endothelium as migrating leukocytes cross it (somewhat analogous to the intermediate compartment in the testis), thereby maintaining barrier integrity Mamdouh et al, 2009;Nourshargh et al, 2010;Rothlein et al, 1986). A soluble form of ICAM-1 (sICAM-1), which is comprised of the entire or a portion of the extracellular domain of ICAM-1 and most likely derived from proteolytic cleavage of membrane-bound ICAM-1, has also been described to have important biological functions in other epithelia (Gearing et al, 1992;Lawson and Wolf, 2009;Marlin et al, 1990;Rothlein et al, 1991;van de Stolpe and van der Saag, 1996;Witkowska and Borawska, 2004). Herein, we show that Sertoli cell surfaceassociated ICAM-1 enhanced BTB function by facilitating crosstalk among different junction types, illustrating that ICAM-1 is working below spermatocytes to strengthen barrier function during stages VIII-XI of the seminiferous epithelial cycle.…”

Section: Introductionmentioning

confidence: 99%

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

Xiao

Cheng

Mruk

2012

Journal of Cell Science

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SummaryThe mechanism underlying the movement of preleptotene/leptotene spermatocytes across the blood-testis barrier (BTB) during spermatogenesis is not well understood largely owing to the fact that the BTB, unlike most other blood-tissue barriers, is composed of several co-existing and co-functioning junction types. In the present study, we show that intercellular adhesion molecule-1 [ICAM-1, a Sertoli and germ cell adhesion protein having five immunoglobulin (Ig)-like domains, in addition to transmembrane and cytoplasmic domains] is a regulator of BTB integrity. Initial experiments showed ICAM-1 to co-immunoprecipitate and co-localize with tight junction and basal ectoplasmic specialization proteins such as occludin and N-cadherin, which contribute to BTB function. More importantly, overexpression of ICAM-1 in Sertoli cells in vitro enhanced barrier function when monitored by transepithelial electrical resistance measurements, illustrating that ICAM-1-mediated adhesion can promote BTB integrity. On the other hand, overexpression of a truncated form of ICAM-1 that consisted only of the five Ig-like domains (sICAM-1; this form of ICAM-1 is known to be secreted) elicited an opposite effect when Sertoli cell barrier function was found to be perturbed in vitro; in this case, sICAM-1 overexpression resulted in the downregulation of several BTB constituent proteins, which was probably mediated by Pyk2/p-Pyk2-Y402 and c-Src/pSrc-Y530. These findings were expanded to the in vivo level when BTB function was found to be disrupted following sICAM-1 overexpression. These data illustrate the existence of a unique mechanism in the mammalian testis where ICAM-1 can either positively or negatively regulate BTB function.

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Soluble Forms of Vascular Adhesion Molecules, E‐Selectin, ICAM‐1, and VCAM‐1: Pathological Significance

Cited by 394 publications

References 31 publications

Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis

Deactivation of vascular endothelium by monoclonal anti–tumor necrosis factor α antibody in rheumatoid arthritis

Hydroxyurea downregulates endothelin-1 gene expression and upregulates ICAM-1 gene expression in cultured human endothelial cells

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

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