title: Mechanisms of glomerular injury in experimental immune nephritis. II. Effect of a platelet activating factor receptor antagonist in an autologous nephritis model.
abstract: The role of Platelet Activating Factor (PAF) in experimental immune glomerulonephritis was assessed by administering the specific PAF receptor antagonist CV-3988 to inbred LEW rats with the Accelerated Autologous Nephrotoxic Serum Nephritis (AA-NTSN). Intravenous administration of CV-3988 caused a marked and sustained reduction in albuminuria and renal histopathological changes. Conversely, although CV-3988 appeared to modulate the fall in glomerular filtration rate (GFR) in the AA-NTSN, this trend was not statistically significant. Renal glomeruli isolated on day 1 after nephritis induction spontaneously released 16.9 +/- 2.2 ng of PAF per 200 glomeruli, while in glomeruli of healthy rats this secretion was virtually undetectable. The administration of CV-3988 to rats with AA-NTSN did not affect the following: binding of intravenously injected sheep anti-rat glomerular basement membrane (GBM) antibody; levels of autologous antibody to sheep immunoglobulin G; the functional integrity of circulating neutrophils. We conclude that local PAF generation and release is intimately linked with the pathogenesis of glomerular injury in this form of immune disease.
authors.affiliation: Department of Nephrology, Medical Academy, Wrocław, Poland.
authors.forename: Z W
authors.initials: ZW
authors.lastname: Hruby
authors.forename: R P
authors.initials: RP
authors.lastname: Lowry
authors.forename: R D
authors.initials: RD
authors.lastname: Forbes
authors.forename: D
authors.initials: D
authors.lastname: Blais
mesh_terms: D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007678:Kidney Glomerulus / Q000293:injuries* / Q000473:pathology; D008297:Male; D009393:Nephritis / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000502:physiology; D010980:Platelet Membrane Glycoproteins; D051381:Rats; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled
chemical_list: D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C037913:CV 3988; D003404:Creatinine