Increased oxygen radical and eicosanoid formation in immune-mediated mesangial cell injury.
To evaluate whether monocytes/macrophages derived from glomeruli could be a source of increased eicosanoid and free oxygen radical formation in glomerular disease, monocytes/macrophage (M/M) were isolated from nephritic glomeruli and their in vitro generation of eicosanoids and superoxides were measured. Glomerular immune injury was induced by i.v. injection of a rabbit-anti-rat thymocyte antiserum (ATS). Kidneys were removed two, five, and 24 hours, and three and eight days after ATS. Adhesive glomerular macrophages were obtained by isolation of glomeruli, enzymatic digestion and incubation of the single cell suspensions in culture dishes. O2-production was evaluated by superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome C; PGE2 and TxB2 release was assessed by direct RIA. Glomerular macrophage infiltration was maximal 24 hours after intravenous antibody (35.9 +/- 5.1 M/M per glomerulus). In vitro production of superoxide was significantly enhanced (P less than 0.001) five hours after ATS administration (51.6 +/- 4.4 nmol O2/10(6) MM/hr), when compared with M/M from controls (30.4 +/- 2.0 nmol O2/10(6) MM/hr). TxB2 formation of glomerular M/M was increased (P less than 0.001) two hours and five hours after ATS administration (1056 +/- 75 and 1182 +/- 112 pg TxB2/10(6) MM/hr) compared with controls (390 +/- 34 pg TxB2/10(6) MM/hr). PGE2 synthesis, however, was decreased (P less than 0.01) at five hours after ATS (629 +/- 43 pg PGE2/10(6) MM/hr) compared with controls (950 +/- 125 pg PGE2/10(6) MM/hr). Furthermore, there was release of leukotriene B4 (LTB4) in monocytes of nephritic glomeruli five hours after ATS administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Oberle
G P
GP
Department of Medicine, University of Frankfurt a.M., Germany.
Niemeyer
J
J
Thaiss
F
F
Schoeppe
W
W
Stahl
R A
RA
D000818:Animals; D015777:Eicosanoids / Q000096:biosynthesis*; D005609:Free Radicals; D005920:Glomerular Mesangium / Q000276:immunology / Q000293:injuries* / Q000378:metabolism; D066298:In Vitro Techniques; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D009393:Nephritis / Q000209:etiology; D010100:Oxygen / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D015777:Eicosanoids; D005609:Free Radicals; D011453:Prostaglandins; D010100:Oxygen