Document Detail


Effect of a platelet-activating factor (PAF) receptor antagonist on hyperacute xenograft rejection; evaluation in a pig kidney-human blood xenoperfusion model.
MedLine Citation:
PMID:  9697996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In 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 = 5), human blood (HETER group, n = 6) or human blood plus BN 52021 (BN group, n = 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, CH50, 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.
Authors:
J M Cruzado; J Torras; M Riera; N Lloberas; I Herrero; E Condom; J Martorell; J Alsina; J M Grinyó
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  113     ISSN:  0009-9104     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-08-21     Completed Date:  1998-08-21     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  136-44     Citation Subset:  IM    
Affiliation:
Department of Nephrology, Hospital de Bellvitge, Ciutat Sanitaria i Universitaria de Bellvitge, Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Diterpenes*
Fibrinolytic Agents / therapeutic use*
Fluorescent Antibody Technique, Indirect
Ginkgolides
Graft Rejection / drug therapy*,  immunology*
Humans
Kidney / metabolism
Kidney Function Tests
Kidney Transplantation*
Lactones / therapeutic use*
Male
P-Selectin / metabolism
Perfusion
Peroxidase / metabolism
Platelet Activating Factor / antagonists & inhibitors*
Platelet Membrane Glycoproteins / antagonists & inhibitors*
Receptors, Cell Surface*
Receptors, G-Protein-Coupled*
Swine
Transplantation, Heterologous
Chemical
Reg. No./Substance:
0/Diterpenes; 0/Fibrinolytic Agents; 0/Ginkgolides; 0/Lactones; 0/P-Selectin; 0/Platelet Activating Factor; 0/Platelet Membrane Glycoproteins; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/platelet activating factor receptor; 99796-69-7/ginkgolide B; EC 1.11.1.7/Peroxidase
Comments/Corrections

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