Mechanisms of glomerular injury in experimental immune nephritis. II. Effect of a platelet activating factor receptor antagonist in an autologous nephritis model.
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.
Hruby
Z W
ZW
Department of Nephrology, Medical Academy, Wrocław, Poland.
Lowry
R P
RP
Forbes
R D
RD
Blais
D
D
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
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