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Research Article Free access | 10.1172/JCI113542

Increased leukotriene B4 synthesis in immune injured rat glomeruli.

M A Rahman, M Nakazawa, S N Emancipator, and M J Dunn

Department of Medicine, Hines Veterans Administration Hospital, Illinois 60141.

Find articles by Rahman, M. in: PubMed | Google Scholar

Department of Medicine, Hines Veterans Administration Hospital, Illinois 60141.

Find articles by Nakazawa, M. in: PubMed | Google Scholar

Department of Medicine, Hines Veterans Administration Hospital, Illinois 60141.

Find articles by Emancipator, S. in: PubMed | Google Scholar

Department of Medicine, Hines Veterans Administration Hospital, Illinois 60141.

Find articles by Dunn, M. in: PubMed | Google Scholar

Published June 1, 1988 - More info

Published in Volume 81, Issue 6 on June 1, 1988
J Clin Invest. 1988;81(6):1945–1952. https://doi.org/10.1172/JCI113542.
© 1988 The American Society for Clinical Investigation
Published June 1, 1988 - Version history
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Abstract

We examined glomerular synthesis of the 5-lipoxygenase metabolite, LTB4, in normal and immune-injured rat glomeruli. Glomeruli isolated from normal rats and from rats with nephrotoxic serum nephritis (NSN), passive Heymann nephritis (PHN) and cationic bovine gamma globulin (CBGG)-induced glomerulonephritis were incubated with the calcium ionophore A23187 (3 microM). Lipids in the glomeruli and media were extracted with ethyl acetate, and were purified and fractionated by HPLC. Immunoreactive-LTB4 (i-LTB4) was determined by radioimmunoassay on HPLC fractions with a detection limit of 50 pg of i-LTB4. A large peak of i-LTB4 that comigrated with authentic LTB4 was found exclusively in glomeruli isolated from the CBGG-injected rats. Addition of the lipoxygenase inhibitor BW755C (50 micrograms/ml) to glomerular incubation resulted in greater than 90% inhibition of i-LTB4. Synthesis of i-LTB4 by glomeruli from normal, NSN and PHN rats was undetectable. Glomerular LTB4 synthesis by CBGG-injected rats was confirmed by radiometric HPLC and by gas chromatography mass-spectroscopy (GC-MS) analysis. In order to rule out synthesis of LTB4 by neutrophils entrapped in the glomeruli, a group of rats received 1,000 rad total body x irradiation, with shielding of the kidneys before induction of CBGG glomerulonephritis. Despite greater than 95% reduction in total leukocyte count, glomerular synthesis of LTB4 remained enhanced. Augmented glomerular synthesis of the proinflammatory lipid, LTB4, in the CBGG model of glomerular disease could have an important role in the development of glomerular injury and proteinuria.

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