title: Intraglomerular platelet aggregation and experimental glomerulonephritis.
abstract: Oxygen free radical production inhibits ADPase-mediated antithrombotic action. Different forms of experimental glomerulonephritis (GN) are characterized by early glomerular influx of inflammatory cells and thrombus formation. The causal relationship of these inflammatory events is obscure. Previous studies have shown that glomerular ADPase in the rat kidney may function as a potent antithrombotic principle, whereas this enzyme is highly sensitive for oxygen free radicals. To study whether O2- producing inflammatory cells are able to induce intraglomerular thrombosis via impairment of ADPase, we investigated influx of inflammatory cells in relation to glomerular ADPase activity and platelet aggregation in three models of GN. In two of these models (anti-Thy1 and anti-GBM GN) influx of neutrophils and thrombus formation occurs, whereas in anti-FX1A nephritis this aspect of the inflammatory phase is not present. The results show a relationship between influx of oxygen free radical-producing cells, reduction of glomerular ADPase activity and increased platelet aggregation. Moreover, it is shown that impairment of glomerular ADPase and increased platelet aggregation in anti-Thy1 and anti-GBM GN could be reduced by treatment with superoxide dismutase and catalase. The demonstration that activated neutrophils perfused ex vivo in the rat kidney can directly affect glomerular ADPase and antithrombotic potential in an O2- dependent manner, further supports the proposed sequence of events; oxygen free radicals produced by activated neutrophils reduce glomerular ADPase activity, leading to facilitation of thrombus formation.
authors.affiliation: Department of Pathology, University of Groningen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Poelstra
authors.forename: M J
authors.initials: MJ
authors.lastname: Hardonk
authors.forename: J
authors.initials: J
authors.lastname: Koudstaal
authors.forename: W W
authors.initials: WW
authors.lastname: Bakker
mesh_terms: D000818:Animals; D001081:Apyrase / Q000378:metabolism; D005260:Female; D005609:Free Radicals; D005921:Glomerulonephritis / Q000097:blood* / Q000276:immunology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000503:physiopathology*; D009504:Neutrophils / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity; D010974:Platelet Aggregation / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013927:Thrombosis / Q000209:etiology
chemical_list: D005609:Free Radicals; D001081:Apyrase; D010100:Oxygen