title: Interstitial mononuclear cell infiltrates in experimental nephrosis: effect of PAF antagonist.
abstract: Rats receiving a single injection of either aminonucleoside of puromycin (PAN, 10 mg/100 g) or Adriamycin (ADR, 7.5 mg/kg) develop heavy proteinuria and tubulointerstitial nephritis. Interstitial mononuclear cells were markedly more intense in PAN- than in ADR-treated rats. The composition of cell infiltrates was characterised in frozen kidney sections using an immunoperoxidase staining method and a panel of specific monoclonal antibodies. The severe mixed cellular lesions observed in the PAN model on day 14 were dominated by ED1+ macrophages, OX6+ Ia-interstitial and OX8+ T-cytotoxic/suppressor cell surface markers. A similar but more discrete ADR-interstitial cell accumulation was observed on day 11 of the experiment. A correlation existed in the PAN model between the severity of interstitial nephritis and the degree of proteinuria. In contrast, there was no such correlation in ADR nephrosis. Administration of PAF antagonist (BN 52021), started on the first day and continued throughout the 4 weeks of the experiment, induced in both ADR and PAN-treated rats a partial reduction in the number of interstitial cell infiltrates. Glomeruli from normal control rats incubated with 3H acetate, substrate for lyso-PAF: acetyl-CoA acetyltransferase and ADR stimulated PAF generation. Although the precise mechanism of interstitial cell accumulation in these two models of nephrosis are still unknown, our results suggest that PAF could be an important factor involved in interstitial cell recruitment.
authors.affiliation: Department of Pathology, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: F M
authors.initials: FM
authors.lastname: Mampaso
authors.forename: J
authors.initials: J
authors.lastname: Egido
authors.forename: J C
authors.initials: JC
authors.lastname: Martínez-Montero
authors.forename: T
authors.initials: T
authors.lastname: Bricio
authors.forename: E
authors.initials: E
authors.lastname: González
authors.forename: M E
authors.initials: ME
authors.lastname: Cobo
authors.forename: E
authors.initials: E
authors.lastname: Pirotzky
authors.forename: P
authors.initials: P
authors.lastname: Braquet
authors.forename: L
authors.initials: L
authors.lastname: Hernando
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D004195:Disease Models, Animal; D004224:Diterpenes; D004317:Doxorubicin; D046934:Ginkgolides; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced / Q000473:pathology; D011691:Puromycin; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000085:Acetates; D000911:Antibodies, Monoclonal; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D011691:Puromycin; D004317:Doxorubicin; C045856:ginkgolide B