Platelet-activating factor receptor blocking reduces proteinuria and improves survival in lupus autoimmune mice.
Platelet-activating factor (PAF) has been suggested recently to play an important role in immune glomerulonephritis, favoring the formation of immune deposits in glomeruli and contributing to the local inflammatory reaction. Here we sought to investigate whether urinary PAF excretion was modified in New Zealand Black x New Zealand White mice a model of genetically determined immune complex disease which mimics systemic lupus in humans and whether changes in PAF urinary excretion values correlated with the extent of proteinuria. To clarify the possible "in vivo" relevance of these findings we evaluated whether PAF receptor antagonist has any influence on the evolution of renal disease and survival of these mice. Our results showed that: 1) in lupus mice urinary PAF excretion increased progressively with age in New Zealand Black x White; 2) the increase in PAF excretion correlated with the severity of proteinuria; and 3) the chronic administration of a PAF receptor antagonist [L-659,989 [(+/- )-trans-2-(3-methoxy-5-methylsulfonyl-4-propoxyphenyl)-5- (3,4,5-trimethoxyphenyl)tetrahydrofuran]] starting from 26 weeks of age significantly delayed the onset of proteinuria and prolonged survival.
Morigi
M
M
Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
Macconi
D
D
Riccardi
E
E
Boccardo
P
P
Zilio
P
P
Bertani
T
T
Remuzzi
G
G
D000818:Animals; D001806:Blood Urea Nitrogen; D005260:Female; D005663:Furans / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D051379:Mice; D008814:Mice, Inbred NZB; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology / Q000652:urine; D010980:Platelet Membrane Glycoproteins; D011507:Proteinuria / Q000188:drug therapy*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled; D015996:Survival Rate
D005663:Furans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C054893:L 659989