leukotriene-b4 and Nephritis

Topics: Animals; Arachidonic Acids; Arthritis, Rheumatoid; Edema; Eosinophils; Guinea Pigs; Humans; Hypersensitivity; Leukotriene B4; Mast Cells; Mice; Muscle Contraction; Nephritis; Prostaglandin D2; Prostaglandins; Prostaglandins D; Rabbits; Rats; Receptors, Fc; Receptors, IgE; Receptors, Immunologic; SRS-A; Thromboxanes

The aim was to explore the correlations of leukotriene B4 (LTB4) and 25-hydroxyvitamin D3 [25(OH)D3] levels with disease severity in children with Henoch-Schonlein purpura (HSP).. A total of 260 HSP children admitted from January 2017 to December 2018 were selected, and 60 healthy children physically examined in the same period were enrolled as controls. The results of general laboratory tests and expression levels of leukotriene B4 (LTB4) and 25-hydroxyvitamin D3 [25(OH)D3] were compared. The correlations of LTB4 and 25(OH)D3 with immunoglobulin A (IgA) were statistically analyzed, and the expression levels of LTB4 and 25(OH)D3 were compared between Henoch-Schonlein purpura nephritis (HSPN) group and non-Henoch-Schonlein purpura nephritis (NHSPN) group. The optimal cutoff values of LTB4 and 25(OH)D3 to predict HSP were analyzed by receiver operating characteristic (ROC) curves, based on which they were divided into low-, intermediate-, and high-risk groups. The length of hospital stay and recurrence rate within 6 months were compared.. The levels of white blood cell count, platelets, C-reactive protein, IgA, IgM, IgE, complement C3, and LTB4 were significantly higher and 25(OH)D3 was lower in HSP group than those in control group (p < 0.05). IgA, LTB4, and 25(OH)D3 levels were independent risk factors for HSP (p < 0.05). LTB4 was positively correlated with IgA (p < 0.05), and 25(OH)D3 was negatively correlated with IgA (p < 0.05). LTB4 level was significantly higher and 25(OH)D3 level was lower in HSPN group than those in NHSPN group (p < 0.05). The optimal cutoff values of LTB4 and 25(OH)D3 were 27.82 pg/mL and 22.10 ng/mL, respectively, the length of hospital stay gradually increased in low-, intermediate-, and high-risk groups, and the recurrence rates within 6 months were 14.2%, 31.5%, and 39.6%, respectively (p < 0.05).. LTB4 level increases and 25(OH)D3 level decreases in children with HSP, and the expression levels are significantly correlated with disease severity, suggesting predictive values for prognosis.

Topics: Calcifediol; Child; Humans; IgA Vasculitis; Immunoglobulin A; Leukotriene B4; Nephritis; Severity of Illness Index

We studied leukotriene B4 (LTB4) synthesis in isolated glomeruli of rats with nephrotoxic serum nephritis. This nephritis was induced in male Sprague Dawley rats by injecting one proteinuric dose of nephrotoxic serum (rabbit anti-rat-GBM serum) after prior immunization of the rats with rabbit IgG. Histological and analytical examinations were performed in kidneys perfused until free of blood 6, 12, 24, 48 and 72 hours after induction of the disease. To investigate LTB4 production, glomeruli were isolated and incubated for one hour in the presence of Ca++-ionophore A23187. The supernatants were analyzed for LTB4. The peak comigrating on reverse-phase high performance liquid chromatography (RP-HPLC) with reference LTB4 was isolated. The ethyl ester trimethylsilyl ether derivative of this peak was analyzed by gaschromatography-mass spectrometry (GC/MS). Identical spectra of the glomerular samples and of reference LTB4 in the positive and in the negative ion chemical ionization mode provided unequivocal evidence that the substance released from the nephritic glomeruli was indeed LTB4. Six hours after injection of nephrotoxic serum, glomerular LTB4 release was highest with 5.52 +/- 0.50, then declining to 2.20 +/- 0.10 ng/mg glomerular protein at 12 hours. At 24, 48 and 72 hours no statistically significant difference from control animals was found. No metabolism of LTB4 to 20-hydroxy- or 20-carboxy-LTB4 was detected during the incubation period. Albuminuria developed during the first 24 hours after nephrotoxic serum challenge and rose steadily throughout the observation period up to 277 +/- 25 mg/24 hr after 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Albuminuria; Animals; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Granulocytes; Kidney Glomerulus; Leukotriene B4; Male; Nephritis; Rats; Rats, Inbred Strains

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.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Female; Fluorescent Antibody Technique; Gas Chromatography-Mass Spectrometry; Glomerulonephritis; Kidney Glomerulus; Leukotriene B4; Male; Microscopy, Electron; Nephritis; Neutrophils; Pyrazoles; Rabbits; Radioimmunoassay; Rats; Rats, Inbred Strains