Expression and functional characterization of a soluble form of vascular cell adhesion molecule 1

Lobb, Roy R.; Chi-Rosso, G; Leone, Diane R.; Rosa, Margaret D.; Newman, Barbara M.; Luhowskyj, Stefan; Osborn, Laurelee; Schiffer, Steffen; Benjamin, Christopher D.; Dougas, Irene; Hession, Catherine; Chow, Pingchang

doi:10.1016/0006-291x(91)91063-i

Cited by 102 publications

(76 citation statements)

References 15 publications

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“…In the same way, a large study reported no association between hormone replacement therapy in postmenauposal women and asthma severity. 14 sE-selectin is reported to be only a weak inhibitor of E-selectin-mediated adhesion, 15 while it may have cytokine-like functions that activate the polymorphonuclear cell CD11b integrin receptor, serving as a chemoattractant. 16 Furthermore, Th-1 lymphocytes, but not Th-2, are able to bind to E-selectin.…”

Section: Discussionmentioning

confidence: 99%

“…9 It has also been reported that sE-selectin levels are increased in autoimmune diseases. 10 There is evidence that endothelin 1, a mediator released by activated EC, is involved in asthmatic bronchial inflammation and remodeling pathways. 11 The higher levels of sE-selectin could be influenced by the estrogen receptor that accumulates in the cytoplasm of smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

“…19 VCAM-1 is expressed on EC, epithelia, macrophages, and dendritic cells. 15 Soluble forms of VCAM-1 are shed from cytokine-activated EC. 1 Serum sVCAM-1 levels in our patients were increased compared with healthy controls, but were similar in mild/ moderate and severe asthmatic patients.…”

Section: Discussionmentioning

confidence: 99%

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Elevation of serum soluble E‐selectin and VCAM‐1 in severe asthma

Hamzaoui

Ammar

et al. 2001

Mediators of Inflammation

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Objective: To investigate the significance of circulating adhesion molecules associated with leucocyteendothelial cell interactions in asthma, serum levels of soluble E (sE)-selectin, soluble P (sP)-selectin, soluble L (sL)-selectin, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in mild, moderate and severe asthma. Method: Serum levels of sE-selectin, sP-selectin, sLselectin, and sVCAM-1 were measured in 32 women with asthma and 30 healthy donors using an enzymelinked immunosorbent assay method. Twenty patients were suffering from severe asthma, and 12 from mild/moderate asthma. Results: Serum sE-selectin and sVCAM-1 levels from patients with asthma were significantly higher than those observed in healthy donors (p < 0.01). The levels of sP-selectin were the same as those of controls. The level of sE-selectin exhibited an important increase in the severe asthmatic patients compared with mild/moderate asthma (p < 0.01). The sVCAM-1 level was increased in severe asthma when compared with healthy controls. There was no correlation between the levels of soluble selectins and the age of the patients. A significant correlation was found between sE-selectin and sVCAM-1 levels. Conclusion: These data indicate that circulating soluble forms of the selectins may have different kinetics during the clinical course of asthma, suggesting that they may reflect different inflammatory pathways in severe asthma. Both sVCAM-1 and sE-selectin may be useful immunological markers for monitoring disease activity in asthma.Key words: Asthma, Inflammation, Selectins IntroductionAdherence of leucocytes to endothelial cells (EC) is a primordial event in the sequence of inflammatory response. Specific cell adhesion molecules, expressed on the surface of leucocytes and/or EC, have been identified. As an initial event during inflammation, leucocytes in the blood stream roll along EC with loose contact, mediated by E-selectin, P-selectin and L-selectin. 1 In the inflammation phase, activation of leucocyte integrins occurs with expression of immunoglobulin-like adhesion proteins on EC, including intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1). The leucocytes that are tightly bound to EC then migrate into the subendothelial tissue. Soluble forms of these adhesion molecules are released in circulation. Serum levels may be increased in several inflammatory diseases, and particularly in asthma. These circulating forms may be biologically active. 2 Asthma is known as a bronchial chronic inflammatory disorder. 3 Immunological abnormalities during asthma are characterized by marked activation of the immune system, leading to increased cytokine production by activated effector cells and the induction of antigen expression on EC. 4 The factors modulating the activation and recruitment of circulating inflammatory cells to the lung remain partially unknown, but an early step in this process is the interaction of adhesion molecules on circulating cells with those on EC. 5 Severe asthma is supposed t...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Elevation of serum soluble E‐selectin and VCAM‐1 in severe asthma

Hamzaoui

Ammar

et al. 2001

Mediators of Inflammation

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“…However, the effect of TNFa on the release of ICAM-1 and VCAM-1 from other cell types (such as fibroblasts) has not been studied. The possible in vivo roles of soluble adhesion molecules are, at present, unclear, although immobilized soluble VCAM-1 and E-selectin have been found to support the binding of human leukocytes and leukocyte cell lines (20,32,33). More recently, soluble E-selectin and VCAM-1 were demonstrated to promote angiogenesis in rat cornea and to induce chemotaxis of human endothelial cells (34), which may be of particular relevance in RA, since angiogenesis contributes significantly to the pathogenesis of the disease state (35).…”

Section: Discussionmentioning

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

118

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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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“…16 sE-selectin is also present in serum but at low concentrations. 17 Although a clear physiological role for this protein has not been defined, sE-selectin may be protective against murine nephritis. 18 Genome-wide linkage studies indicate that SLE is inherited as a complex trait.…”

Section: Introductionmentioning

confidence: 99%

No association between E- and L-selectin genes and SLE: soluble L-selectin levels do correlate with genotype and a subset in SLE

et al. 2005

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Altered function of selectin glycoprotein adhesion molecules may modulate severity and organ-specific manifestations of autoimmune and inflammatory disease via changes in leukocyte trafficking. Serum concentrations of selectin molecules have been suggested as useful biomarkers in systemic lupus erythematosus (SLE). We identified increased levels of soluble L-selectin (sL-selectin), but not soluble E-selectin (sE-selectin) in 278 European-Caucasian lupus patients compared to 230 healthy siblings (P ¼ 0.002). sL-selectin levels were markedly elevated in patients with IgG antiphospholipid autoantibodies (P ¼ 0.002), suggesting that perhaps sL-selectin defines a subgroup of lupus with vasculopathy. sL-selectin level was also influenced by two L-selectin polymorphisms: 665C4T, F206L in the epidermal growth factor-like domain (P ¼ 0.015) and rs12938 in the 3 0 -untranslated region (P ¼ 0.06). Having shown increased sL-selectin levels in lupus patients, we used genetics to investigate whether this was a secondary phenomena or the result of an underlying genetic mechanism. The inheritance of nine single-nucleotide polymorphisms (SNP) spanning the selectin locus was tested in 523 UK simplex SLE families. No association with SLE, or related phenotypes, was evident with any single SNP, or haplotype in family-based tests of association. Selectin polymorphisms are, therefore, unlikely to be independent factors in SLE susceptibility.

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Expression and functional characterization of a soluble form of vascular cell adhesion molecule 1

Cited by 102 publications

References 15 publications

Elevation of serum soluble E‐selectin and VCAM‐1 in severe asthma

Elevation of serum soluble E‐selectin and VCAM‐1 in severe asthma

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

No association between E- and L-selectin genes and SLE: soluble L-selectin levels do correlate with genotype and a subset in SLE

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