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.
M A Rahman, M Nakazawa, S N Emancipator, M J Dunn
Title and authors | Publication | Year |
---|---|---|
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Brenner and Rector's The Kidney | 2012 |
Role of leukotriene B4 in accelerated hyperlipidaemic renal injury
K Doi, Y Hamasaki, E Noiri, K Nosaka, T Suzuki, A Toda, T Shimizu, T Fujita, A Nakao |
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Annual Reports in Medicinal Chemistry
JJ Liu, TW Lee |
Annual Reports in Medicinal Chemistry Volume 46 | 2011 |
5-Lipoxygenase and leukotriene A 4 hydrolase expression in primary nephrotic syndrome
A Bakr, S Hawas, S Slem, AA Moniem, T Ghatab, M Tawfik |
Pediatric Nephrology | 2004 |
Detrimental Effects of a High Fat Diet in Early Renal Injury Are Ameliorated by Fish Oil in Han:SPRD-cy Rats
J Lu, N Bankovic-Calic, M Ogborn, MH Saboorian, HM Aukema |
The Journal of nutrition | 2003 |
Induction of Nephrotoxic Serum Nephritis in Inbred Mice and Suppressive Effect of Colchicine on the Development of this Nephritis
S Chen, T Mukoyama, N Sato, SI Yamagata, Y Arai, N Satoh, S Ueda |
Pharmacological Research | 2002 |
Immunohistochemical localization of guinea-pig leukotriene B4 12-hydroxydehydrogenase/15-ketoprostaglandin 13-reductase
T Yamamoto, T Yokomizo, A Nakao, T Izumi, T Shimizu |
European Journal of Biochemistry | 2001 |
Leukotriene B 4 Receptor: Cloning and Intracellular Signaling
T Yokomizo, K Masuda, K Kato, A Toda, T Izumi, T Shimizu |
American journal of respiratory and critical care medicine | 2000 |
Advances in Eicosanoid Research
CN Serhan, HD Perez |
2000 | |
Ubiquitous localization of leukotriene A4 hydrolase in the rat nephron
A Nakao, T Watanabe, N Ohishi, A Toda, K Asano, S Taniguchi, K Nosaka, E Noiri, T Suzuki, T Sakai, K Kurokawa, T Shimizu, S Kimura |
Kidney International | 1999 |
Transfection of rat kidney with human 15-lipoxygenase suppresses inflammation and preserves function in experimental glomerulonephritis
KA Munger, A Montero, M Fukunaga, S Uda, T Yura, E Imai, Y Kaneda, JM Valdivielso, KF Badr |
Proceedings of the National Academy of Sciences | 1999 |
Effect of Estradiol and Progesterone on the Low-Dose Endotoxin-Induced Glomerular Inflammatory Response of the Female Rat
MM Faas, WW Bakker, N Valkhof, GA Schuiling |
American Journal of Reproductive Immunology | 1999 |
The Leukotriene B4 Receptor Antagonist ONO-4057 Inhibits Nephrotoxic Serum Nephritis in WKY Rats
S Suzuki, T Kuroda, JI Kazama, N Imai, H Kimura, M Arakawa, F Gejyo |
Journal of the American Society of Nephrology : JASN | 1999 |
Cytokines, Growth Factors, and Other Inflammatory Mediators in Glomerulonephritis
A Papayianni |
Renal Failure | 1996 |
Leukotriene A4 hydrolase and leukotriene B4 metabolism
T Yokomizo, N Uozumi, T Takahashi, K Kume, T Izumi, T Shimizu |
Journal of Lipid Mediators and Cell Signalling | 1995 |
Lipoxygenase Products in Normal and Diseased Glomeruli
KF Badr, FG Lakkis |
Annals of the New York Academy of Sciences | 1994 |
Renal complications of nonsteroidal anti-inflammatory drugs
D Schlondorff |
Kidney International | 1993 |
Phospholipid derived mediators and glomerulonephritis
EN Wardle |
Mediators of Inflammation | 1993 |
Rat mesangial cell lysis in vitro is induced by cationic polypeptides
JA Broestl, SN Emancipator |
The American Journal of Pathology | 1993 |
Enzymatic inactivation of leukotriene B4 by a novel enzyme found in the porcine kidney. Purification and properties of leukotriene B4 12-hydroxydehydrogenase
T Yokomizo, T Izumi, T Takahashi, T Kasama, Y Kobayashi, F Sato, Y Taketani, T Shimizu |
The Journal of biological chemistry | 1993 |
Role of the 5-lipooxygenase pathway in obstructive nephropathy
AA Reyes, J Lefkowith, J Pippin, S Klahr |
Kidney International | 1992 |
Fifteen-S-hydroxyeicosatetraenoic acid (15-S-HETE) specifically antagonizes the chemotactic action and glomerular synthesis of leukotriene B4 in the rat
DB Fischer, JW Christman, KF Badr |
Kidney International | 1992 |
Mesangial cell immune injury. Synthesis, origin, and role of eicosanoids
EA Lianos, BA Bresnahan, C Pan |
Journal of Clinical Investigation | 1991 |
Enhanced renal leukotriene production in murine lupus: Role of lipoxygenase metabolites
RF Spurney, P Ruiz, DS Pisetsky, TM Coffman |
Kidney International | 1991 |
Involvement of Lipid Mediators in the Pathogenesis of Experimental Nephrosis in Rats: Its Pharmacological Modulation
J Egido, A Ortiz, M Goméz-Chiarri, JL Lerma, A Robles, C Bustos, C Gómez-Guerrero, J Alonso, E González |
Renal Failure | 1991 |
Involvement of thromboxane A2, leukotrienes and free radicals in puromycin nephrosis in rats
Y Shibouta, Z Terashita, Y Imura, A Shino, M Kawamura, K Ohtsuki, S Ohkawa, K Nishikawa, Y Fujiwara |
Kidney International | 1991 |
Lipoxygenases and their Products
MA Wasserman, EF Smith, DC Underwood, MA Barnette |
Lipoxygenases and their Products | 1991 |
Cell-Cell Interactions in the Release of Inflammatory Mediators
PY Wong, CN Serhan |
1991 | |
Immunology of Renal Disease
CD Pusey |
1991 | |
Predominant functional roles for thromboxane A2 and prostaglandin E2 during late nephrotoxic serum glomerulonephritis in the rat
K Takahashi, GF Schreiner, K Yamashita, BW Christman, I Blair, KF Badr |
Journal of Clinical Investigation | 1990 |
Endothelial factors in the regulation of renin release
WB Campbell, WL Henrich |
Kidney International | 1990 |
Eicosanoid biosynthesis and role in renal immune injury
EA Lianos |
Prostaglandins, Leukotrienes and Essential Fatty Acids | 1990 |
Human glomerular mesangial cells inactivate leukotriene B4 by reduction into dihydro-leukotriene B4 metabolites
V Kaever, J Bruuns, J Wunder, B Damerau, G Zimmer, J Fauler, K Wessel, J Floege, N Topley, H Radeke, K Resch |
Life Sciences | 1990 |
Leukotriene B4 production in children with steroid-responsive nephrotic syndrome
Y Kikawa, A Nakai, Y Shigematsu, M Sudo, K Kato, S Haruki |
Pediatric Nephrology | 1990 |
Eicosanoids and the modulation of glomerular immune injury
EA Lianos |
Kidney International | 1989 |
Glomerular leukotriene synthesis in Heymann nephritis
EA Lianos, B Noble, B Hucke |
Kidney International | 1989 |
LTB4 in nephrotoxic serum nephritis in rats
J Fauler, A Wiemeyer, KH Marx, K Kühn, KM Koch, JC Frölich |
Kidney International | 1989 |
Role of arachidonic acid metabolites and reactive oxygen species in glomerular immune-inflammatory process
R Ardaillou, L Baud, J Sraer |
Springer Seminars in Immunopathology | 1987 |