A P-selectin-immunoglobulin G chimera is protective in a rabbit ear model of ischemia-reperfusion

Lee, Wyne Pun; Gribling, Peter; Guzman, Leo De; Ehsani, Niloofar; Watson, Susan R.

doi:10.1016/s0039-6060(05)80068-6

Cited by 18 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The bivalent nature of the molecules increases the binding affinity, and the immunoglobulin chain prolongs the biological half-life in vivo ( 33 ). While there are some well-known examples involving selectins ( 29 , 32 , 34 ), there are few reports on the use of CAMs from other molecular families fused to IgG to block inflammation in vivo ( 33 , 35 ). This may be because most CAMs have a rather low affinity for interaction with their ligands on a molecule-to-molecule basis ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Soluble Domain 1 of Platelet–Endothelial Cell Adhesion Molecule (PECAM) Is Sufficient to Block Transendothelial Migration In Vitro and In Vivo

Liao

Ali

Greene

et al. 1997

The Journal of Experimental Medicine

173

150

View full text Add to dashboard Cite

The inflammatory response involves sequential adhesive interactions between cell adhesion molecules of leukocytes and the endothelium. Unlike the several adhesive steps that precede it, transendothelial migration (diapedesis), the step in which leukocytes migrate between apposed endothelial cells, appears to involve primarily one adhesion molecule, platelet–endothelial cell adhesion molecule (PECAM, CD31). Therefore, we have focused on PECAM as a target for antiinflammatory therapy. We demonstrate that soluble chimeras made of the entire extracellular portion of PECAM, or of only the first immunoglobulin domain of PECAM, fused to the Fc portion of IgG, block diapedesis in vitro and in vivo. Furthermore, the truncated form of the PECAM-IgG chimera does not bind stably to its cellular ligand. This raises the possibility of selective anti-PECAM therapies that would not have the untoward opsonic or cell-activating properties of antibodies directed against PECAM.

show abstract

Section: Discussionmentioning

confidence: 99%

Soluble Domain 1 of Platelet–Endothelial Cell Adhesion Molecule (PECAM) Is Sufficient to Block Transendothelial Migration In Vitro and In Vivo

Liao

Ali

Greene

et al. 1997

The Journal of Experimental Medicine

173

150

View full text Add to dashboard Cite

show abstract

“…Other investigators have combined antibodies to multiple selectins [39,40] or have used responsible for this decrease in fibrin accumulation. Since monocytes express tissue factor on their surface, antibody chimeras, small molecule inhibitors of selectins, with success [41]. However, ours is the first study such inhibition would limit the thrombotic amplification on the surface of existing fibrin.…”

Section: Fig 2 Neutrophil (A) Total Inflammatory Cell (B)mentioning

confidence: 97%

P-Selectin and TNF Inhibition Reduce Venous Thrombosis Inflammation

Wakefield¹,

Strieter²,

Downing³

et al. 1996

Journal of Surgical Research

View full text Add to dashboard Cite

“…[34][35][36] Although selectins are not thought to activate cells directly, they probably facilitate activation by other molecules by immobilising PMNs on the endothelial surface. " Weyrich and colleagues34 have recently reported that adherence of monocytes to endothelial cells via P-selectin (along with exposure to a second stimulus such as platelet activating factor or bacterial lipopolysaccharide) upregulates TNFce and monocyte chemotactic protein-I generation through NF-KB signalling (NF-KB is a transcription factor that binds to the regulatory regions of numerous cytokine, adhesion protein, and growth factor/receptor genes containing the appropriate binding site in their regulatory regions).…”

Section: Role Of Selectins In Inflammationmentioning

confidence: 99%

Mechanisms of the adult respiratory distress syndrome: selectins.

Albert

1995

Thorax

View full text Add to dashboard Cite

The acute lung injury of adult respiratory distress syndrome (ARDS) is characterised by inflammatory cell accumulation and activation in the lung. Selectins are a family of adhesion molecules implicated in leucocyte-endothelial adhesion, whose receptors can exist in a cleaved, soluble form. We investigated whether circulating soluble selectin adhesion molecules, obtained from ARDS at-risk patients, were associated with subsequent ARDS development Eighty two patients, at risk of ARDS, were enrolled from three well-defined groups (multiple trauma, pancreatitis, perforated bowel). Plasma samples were obtained on hospital presentation and soluble L, E, and P selectins were quantified with a sandwich enzyme-linked immunosorbent assay (ELISA). Fourteen patients subsequently developed ARDS. Initial plasma soluble L-selectin (sL-selectin) levels were significantly lower in patients who progressed to ARDS compared to those who did not (p = 0*0001; 95% Cl for mean in ARDS patients as percent of that in non-ARDS patients, 27-61%). Moreover concentrations were lower than in 62 normal volunteers (range 0-37-6*55, median 1 83 ugImL, n = 62), suggesting that a selective reduction of sL-selectin correlates with susceptibility. In addition, a significant correlation was found between low values of sL-selectin and indices of subsequent lung injury including requirement for ventilation (p = 0*0001) and degree of respiratory failure (p=0.0001). A significant correlation was also found between low values of sL-selectin and patient mortality (p = 0*002). These results elucidate the inflammatory cell endothelial interactions in the early stages of ARDS and may be of prognostic value. (Lancet 1994;344:215-9) Early in the course of the adult respiratory distress syndrome (ARDS) -that is, one or two days after the manifestation of respiratory failure -the lung parenchyma is not significantly abnormal and the predominant histological findings are pulmonary oedema and accumulation of polymorphonuclear leucocytes (PMNs) in the pulmonary circulation, interstitium, and alveolar spaces.' The current paradigm by which PMNs are thought to migrate across the vascular endothelial barrier is a multistage process which begins with a loose attachment of endothelial or cell surface molecules (selectins) to receptors on PMNs or on the endothelium resulting in the phenomenon known as PMN "rolling".6 This is followed by a more firm adherence between other cell adhesion molecules (integrins) and their specific ligands that is triggered by various factors including interleukin (IL)-8, platelet activating factor, bacterial wall components, complement products, and, possibly, E (endothelial)-selectin.7-9 Recently, platelet endothelial adhesion molecule (PECAM)-1, another cell adhesion molecule from the immunoglobulin superfamily, has also been linked to PMN transmigration.' 01 Donnelly et all2 have recently measured circulating selectin fragments in the blood of patients at risk for ARDS and found that the level of soluble L-selectin was lower in those ...

show abstract

A P-selectin-immunoglobulin G chimera is protective in a rabbit ear model of ischemia-reperfusion

Cited by 18 publications

References 32 publications

Soluble Domain 1 of Platelet–Endothelial Cell Adhesion Molecule (PECAM) Is Sufficient to Block Transendothelial Migration In Vitro and In Vivo

Soluble Domain 1 of Platelet–Endothelial Cell Adhesion Molecule (PECAM) Is Sufficient to Block Transendothelial Migration In Vitro and In Vivo

P-Selectin and TNF Inhibition Reduce Venous Thrombosis Inflammation

Mechanisms of the adult respiratory distress syndrome: selectins.

Contact Info

Product

Resources

About