Glomerular NO synthase activity in mesangial cell immune injury.
Ex vivo synthesis of nitrite (NO2-) by nephritic glomeruli provides evidence of induction of nitric oxide (NO) in glomerulonephritis (GN). In macrophage-associated GN, the major source is infiltrating macrophages. As induction of NO synthesis has now been shown in cultured mesangial cells, we have examined whether in vivo mesangial proliferation is a source of NO2-. Mesangial proliferative GN was induced by intravenous anti-Thy1.1 (monoclonal antibody ER4). Isolated glomeruli were assayed for NO2- synthesis and macrophage infiltration on day 4 (mesangiolytic phase) and on day 7 (mesangial proliferation). On day 4, but not on day 7, basal NO2- was increased (8.3 +/- 1.8, controls 0.7 +/- 0.1 nmol/2,000 glomeruli/48 h; p = 0.05) and there was macrophage infiltration (60 +/- 15; controls 14 macrophages/glomerulus). At both times NO2- was elevated by exogenous IL1 or LPS, more significantly on day 4 than on day 7. Thus, mesangial proliferative lesions are not a source of basal NO2-, and macrophages are the most likely source. However, NO2- can be induced in mesangial proliferative glomeruli by exogenous stimuli, findings similar to those reported in cultured mesangial cells. Irradiation experiments in normal rats show that stimulated NO2- synthesis is inhibited by macrophage depletion. Therefore in neither normal nor proliferative glomeruli is there evidence for mesangial cell production of NO2-.
Cattell
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V
St. Marys Hospital Medical School, London, UK.
Lianos
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E
Largen
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P
Cook
T
T
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000954:Antigens, Surface / Q000276:immunology; D005920:Glomerular Mesangium / Q000201:enzymology* / Q000276:immunology / Q000293:injuries; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D051381:Rats; D011917:Rats, Inbred Lew; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases