6-ketoprostaglandin-f1-alpha and Autoimmune-Diseases

We analyzed fatty acid make up of cells and organs from autoimmune and immunologically normal mice to determine whether intrinsic differences in composition might be associated with an inflammatory phenotype. Macrophages (MO) isolated from 4-6-week-old MRL lpr/lpr mice were cultured with phorbol ester (PMA), fibroblast growth factor-1 (FGF-1), fibroblast growth factor-2 (FGF-2) and medium control to determine whether these cell signals might induce membrane fatty acid changes. Individual phospholipid analysis showed 8.4- and 5.1-fold increases in phosphatidylcholine arachidonate (20:4) mole % over baseline values following culture with FGF-1 and FGF-2, respectively. Unfractionated analysis on kidney and liver extracts from 4-6 week MRL lpr/lpr, 16-20 week lpr and 12-20 week MRL +/-/+/- mice demonstrated no significant intrastrain fatty acid differences. Higher levels of 20:4 in 4-6 week lpr mice were noted compared to 16-20 week lpr or +/+ mice in kidney, and liver samples (P < 0.05). It is possible that membrane changes precipitated by microenvironmental cytokine concentrations may contribute to the expression of autoimmune disease in this model.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Autoimmune Diseases; Disease Models, Animal; Fatty Acids; Fibroblast Growth Factor 1; Fibroblast Growth Factor 2; Kidney; Leukotriene C4; Liver; Macrophages, Peritoneal; Membrane Lipids; Mice; Mice, Inbred MRL lpr; Phospholipids; Tetradecanoylphorbol Acetate

Repeated subcutaneous (SC) injections of mercuric chloride (MC) in Brown Norway (BN) rats induce an autoimmune glomerulonephritis (GN) due to antiglomerular basement membrane (BM) antibody deposition in the glomeruli. The aim of this study was to investigate the effects on MC-induced autoimmune GN of OKY-046, a selective TXA-synthetase inhibitor herring oil (HO), which is rich in eicosapentaenoic acid (EPA) (5.6%) precursor of the three series of prostaglandins (PGs) and of (inactive) thromboxane (TXA3), and evening primrose oil (EPO), which is rich in linoleic acid (LA) (72%) and gamma-linolenic acid (GLNA) (9%), precursors of the one series of PGs, mainly PGE1, and of (inactive) TXA1. The administration of OKY-046 significantly inhibited proteinuria, partially prevented fibrin thrombi (FT) formation in the glomeruli, decreased urinary TXB, enhanced 6ketoPGF excretion and, increased survival rate of the animals from 60% (group receiving only MC) to 86%. However, OKY-046 did not prevent body weight (BW) loss or the development and deposition of IgG in the glomeruli. Increased intake of HO (80 days prior and throughout the experiment) and avoidance of arachidonic acid (AA) intake produced an effect comparable to that of OKY-046 in the rats. Furthermore, HO significantly inhibited the deposition of IgG in the glomeruli, increased the survival rate of the animals to 100% and further enhanced the increased urinary PGE excretion induced by MC. However, HO did not prevent BW loss in the animals. Increased intake of EPO and avoidance of AA intake produced an effect comparable to that of HO. Additionally, EPO completely prevented BW loss induced by MC in these animals. These findings suggest that the metabolites of AA, EPA and GLNA play an important role either in the development or in the modulation of this model of MC induced GN.

Topics: 6-Ketoprostaglandin F1 alpha; Acrylates; Animals; Autoimmune Diseases; Fatty Acids, Essential; Fatty Acids, Unsaturated; Fish Oils; gamma-Linolenic Acid; Glomerulonephritis; Hypolipidemic Agents; Immunoglobulin G; Linoleic Acids; Mercuric Chloride; Methacrylates; Oenothera biennis; Plant Oils; Prostaglandins E; Proteinuria; Rats; Thromboxane-A Synthase; Thromboxanes

The stability of prostacyclin (PGI2) in whole blood and plasma was studied in vitro by measuring the disappearance rate of labeled prostacyclin during a 37 degrees C incubation. Prostacyclin was assayed using a quantitative chromatographic method. The half-life of PGI2 was 6.3 +/- 0.8 minutes (mean +/- s.d., n = 6) in citrated human whole blood, significantly shorter (p less than 0.001) than the 10.7 +/- 2.3 minute half-life in citrated human plasma (n = 7). Prior freezing and thawing of plasma did not affect the rate of PGI2 hydrolysis. These values, including the prolonged half-life in plasma, were similar in the blood (5.4 +/- 1.8 min, n = 7) and plasma (9.0 +/- 1.9 min, n = 14) of diabetic patients. In plasma samples from patients with thrombotic thrombocytopenic purpura, the half-life of prostacyclin (4.9 +/- 1.0 min, n = 4) was significantly shortened (p less than 0.001) compared to that in plasma from normal volunteers. The stability of prostacyclin in rabbit blood and plasma was also quantified. The PGI2 half-life in citrated rabbit plasma (10.8 +/- 1.1 min, n = 3) was similar to that in citrated human plasma from control subjects. In contrast to the findings in human blood, the half-life of PGI2 in citrated rabbit whole blood (11.7 +/- 3.3 min, n = 4) was not different from the rabbit plasma value. Substitution of EDTA for citrate did not affect the half-life in rabbit blood or plasma.

Topics: 6-Ketoprostaglandin F1 alpha; Anemia, Hemolytic; Animals; Autoimmune Diseases; Brain; Chromatography, High Pressure Liquid; Diabetes Mellitus; Epoprostenol; Half-Life; Humans; Hydrogen-Ion Concentration; Kinetics; Purpura, Thrombotic Thrombocytopenic; Rabbits; Reference Values; Species Specificity; Tritium