Interaction of the Paf antagonist WEB 2086 and its hetrazepine analogues with human platelets and endothelial cells

Korth, Ruth-Maria; Hirafuji, Masahiko; Keraly, C. Lalau; Delautier, Danièle; Bidault, Jocelyne; Benveniste, Jacques

doi:10.1111/j.1476-5381.1989.tb12640.x

Cited by 25 publications

(9 citation statements)

References 42 publications

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“…The ['HI paf binding to T lymphocytes was performed, as previously described [32] by 2-h incubation at 4 "C. T cells (1 x 1O7/ml) were suspended in 1 ml Hepes Buffer containing FAF-HSA (2.5 mg/ml) and [ "] paf binding in the presence of 500 nM unlabeled paf. In some experiments, the specific [3H] paf binding was assessed in the presence of 104'-1()-11 M lyso-paf or Web 2086.The average number of paf-R/cell and the dissociation constant wcre quantified by Scatchard plot analysis of the specific paf equilibrium binding data.…”

Section: Binding Assay Of Radiolabeled Pafmentioning

confidence: 99%

Induction of high‐affinity paf receptor expression during T cell activation

et al. 1992

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Activated human T cells via the CD2 or the CD3 pathways exhibited a higher capacity than resting T lymphocytes to incorporate and metabolize [3H]pafacether (paf) at 37 degrees C. Resting T lymphocytes lacked specific binding capacity for paf, yet high-affinity paf receptors (paf-R) were induced on CD3- or CD2-dependent activation. This up-regulation in the number of paf-R became apparent by day 1 of culture, reached a maximum of about 25,000 sites cell by days 4 to 6 and subsequently declined. Interestingly, human recombinant interleukin-2 in a dose-dependent manner prevented the decrease of high-affinity paf-R expression on T cells. By contrast, the receptor affinity was constant throughout the culture period. Thus, paf-R at different stages of T cell activation were indistinguishable with respect to receptor-ligand interaction, and differed only in their number. Together, these data demonstrate that after activation human T cells develop membrane high-affinity paf-binding sites. They also suggest for the first time that expression of the paf-R are coupled to T cell activation and/or differentiation.

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Section: Binding Assay Of Radiolabeled Pafmentioning

confidence: 99%

Induction of high‐affinity paf receptor expression during T cell activation

et al. 1992

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“…On the other hand, the endothelium expresses PAF receptors [ 37] and consequently is a target for PAF itself [ 38, 39]. PAF, acting on endothelial cells at nanomolar concentrations [ 13], leads to a transient production of diacylglycerol, which activates protein kinase C, and of inositol triphosphate, which mediates the release of calcium from internal stores [ 40, 41].…”

Section: Discussionmentioning

confidence: 99%

Effect of a platelet-activating factor (PAF) receptor antagonist on hyperacute xenograft rejection; evaluation in a pig kidney–human blood xenoperfusion model

Cruzado

Riera

Lloberas

et al. 1998

Clinical and Experimental Immunology

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SUMMARYIn pig to human discordant xenotransplantation, PAF may contribute to the pathogenesis of hyperacute xenograft rejection (HXR). We examined the release of PAF and the effect of a PAF receptor antagonist (BN 52021) on HXR in a pig kidney-human blood xenoperfusion model. Pig kidneys were perfused with porcine blood (AUTO group, n ¼ 5), human blood (HETER group, n ¼ 6) or human blood plus BN 52021 (BN group, n ¼ 4), respectively. In contrast to HETER kidneys that never produced urine and were rejected in 15-30 min, the administration of BN 52021 induced a partial recovery of glomerular filtration rate and allowed kidneys to function until the end of the study. The release of PAF and soluble P-selectin, as well as endothelial P-selectin expression and tissue myeloperoxidase (MPO), were much higher in the HETER than in the AUTO group. HETER and BN kidneys displayed similar natural xenoantibody titres, CH 50 , PAF, soluble P-selectin as well as renal immunoglobulin (IgM, IgG, IgA) and complement (C3, C1q) deposition. However, HETER kidneys displayed a full histologic picture of HXR (mainly interstitial haemorrhage and vascular microthrombi) and BN kidneys had only endothelial cell swelling. Also, BN 52021 administration attenuated glomerular and vascular P-selectin expression and renal tissue MPO activity. We conclude that in the pig kidney-human blood xenoperfusion model, PAF is produced in higher amounts than in the pig kidney-pig blood autologous combination. The administration of BN 52021 exerts a protective effect by means of attenuating the acute inflammatory response and blocking vascular microthrombi formation.

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“…PAF released by EC or by other cells can activate the endothelium itself, by interacting with a specific receptor (Korth et al, 1989) encoded by the same gene as the myeloid cells (Camussi and Bussolino, unpublished results). PAF released by EC or by other cells can activate the endothelium itself, by interacting with a specific receptor (Korth et al, 1989) encoded by the same gene as the myeloid cells (Camussi and Bussolino, unpublished results).…”

Section: Biological Roles Of Paf Produced By Stimulated Endothelial Cmentioning

confidence: 99%

“…PAF as an autocrine molecule and its role in the shape and in the movements of endothelial cells. PAF released by EC or by other cells can activate the endothelium itself, by interacting with a specific receptor (Korth et al, 1989) encoded by the same gene as the myeloid cells (Camussi and Bussolino, unpublished results).…”

Section: Paf As a Paracrine Molecule And Its Role In The Adhesionmentioning

confidence: 99%

Platelet-Activating Factor Produced by Endothelial Cells. A Molecule with Autocrine and Paracrine Properties

Bussolino

Camussi

1995

Eur J Biochem

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Endothelial cells (EC) participate in microenvironment homeostasis by regulating the trafficking of cells and molecules from the bloodstream to the tissues. The 'area codes' used to control the trafficking are adhesion molecules, receptors which pick up external signals, and mediators of cell-to-cell communication. Platelet-activating factor (PAF) is a mediator that belongs to this class of 'area-code' molecules. PAF is an acetylated derivative of phosphatidylcholine which is produced by EC and may act in an autocrine manner. Several stimuli may induce the synthesis of PAF by EC with different time courses. Thrombin, elastase and tumor necrosis factor (TNF) are prototypic molecules inducing very-early, early and delayed PAF synthesis, respectively. These stimuli activate the 'remodelling pathway' which requires the activation of phospholipase A2 and acetyl CoA:1-alkyl-2-lyso-sn-glycero-3-phosphate acetyltransferase. The effects of very-early and early stimuli are mediated by a direct stimulation of this pathway, whereas the action of TNF is mediated by the new synthesis of a serine protease. Stimulated EC produce PAF molecules with both an ether and an ester bond at the sn-1 position, but the former is predominant. The PAF produced is partially exposed on the external membranes and participates in adhesion or migration of neutrophils. PAF released can also stimulate EC themselves, by interacting with a specific receptor. PAF stimulates the migration and the shape change of EC by activating calcium influx and several serine/threonine and tyrosine kinases which regulate the cytoskeleton.

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Interaction of the Paf antagonist WEB 2086 and its hetrazepine analogues with human platelets and endothelial cells

Cited by 25 publications

References 42 publications

Induction of high‐affinity paf receptor expression during T cell activation

Induction of high‐affinity paf receptor expression during T cell activation

Effect of a platelet-activating factor (PAF) receptor antagonist on hyperacute xenograft rejection; evaluation in a pig kidney–human blood xenoperfusion model

Platelet-Activating Factor Produced by Endothelial Cells. A Molecule with Autocrine and Paracrine Properties

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