12-hydroxy-5-8-10-14-eicosatetraenoic-acid and Acute-Disease

Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro- and anti-inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12-HETE and 15-HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12- and 15-HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12- and 15-HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Adult; Body Temperature; Female; Graft Rejection; Humans; Hydroxyeicosatetraenoic Acids; Kidney; Kidney Transplantation; Leukotriene B4; Leukotriene E4; Lipoxygenase; Male; Middle Aged

The peritoneal macrophage (Mphi) is the site of greatest 12/15-lipoxygenase (12/15-LOX) expression in the mouse; however, its immunoregulatory role in this tissue has not been explored. Herein, we show that 12/15-LOX is expressed by 95% of resident peritoneal CD11b(high) cells, with the remaining 5% being 12/15-LOX(-). 12/15-LOX(+) cells are phenotypically defined by high F4/80, SR-A, and Siglec1 expression, and enhanced IL-10 and G-CSF generation. In contrast, 12/15-LOX(-) cells are a dendritic cell population. Resident peritoneal Mphi numbers were significantly increased in 12/15-LOX(-/-) mice, suggesting alterations in migratory trafficking or cell differentiation in vivo. In vitro, Mphi from 12/15-LOX(-/-) mice exhibit multiple abnormalities in the regulation of cytokine/growth factor production both basally and after stimulation with Staphylococcus epidermidis cell-free supernatant. Resident adherent cells from 12/15-LOX(-/-) mice generate more IL-1, IL-3, GM-CSF, and IL-17, but less CCL5/RANTES than do cells from wild-type mice, while Staphylococcus epidermidis cell-free supernatant-elicited 12/15-LOX(-/-) adherent cells release less IL-12p40, IL-12p70, and RANTES, but more GM-CSF. This indicates a selective effect of 12/15-LOX on peritoneal cell cytokine production. In acute sterile peritonitis, 12/15-LOX(+) cells and LOX products were cleared, then reappeared during the resolution phase. The peritoneal lavage of 12/15-LOX(-/-) mice showed elevated TGF-beta1, along with increased immigration of monocytes/Mphi, but decreases in several cytokines including RANTES/CCL5, MCP-1/CCL2, G-CSF, IL-12-p40, IL-17, and TNF-alpha. No changes in neutrophil or lymphocyte numbers were seen. In summary, endogenous 12/15-LOX defines the resident MPhi population and regulates both the recruitment of monocytes/Mphi and cytokine response to bacterial products in vivo.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Animals; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Cells, Cultured; Cytokines; Hydroxyeicosatetraenoic Acids; Immunophenotyping; Inflammation Mediators; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mice, Knockout; Peritonitis; Staphylococcal Infections; Staphylococcus epidermidis

The arylpropionate anti-inflammatory drug, carprofen, was administered intravenously as the racemate at a dose rate of 0.7 mg kg-1 body weight to six Friesian bull calves aged 16-17 weeks. Anti-inflammatory and pharmacokinetic properties were investigated using a tissue cage model of inflammation based on intracaveal injection of the mild irritant, carrageenin. Carprofen displayed enantioselective pharmacokinetics, with the R(-) enantiomer predominating in plasma at all measuring times. Elimination half-life and mean residence time were shorter and volume of distribution and clearance were greater for the S(+) than for the R(-) enantiomer. Penetration of both enantiomers into transudate (non-stimulated tissue cage) was poor but penetration into exudate (carrageenin-stimulated tissue cage) was good. Carprofen failed to reduce exudate concentration of prostaglandin E2 and the reductions in 12-hydroxyeicosatetraenoic acid were non-significant at most sampling times. The long elimination half-life of both R(-) and S(+) carprofen enantiomers and their ready penetration into and slow clearance from inflammatory exudate indicate that the drug is likely to have a long duration of action in calves. The mechanism of action is unknown but it is unlikely to involve inhibition of either cyclooxygenase or 12-lipoxygenase.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Carrageenan; Cattle; Cattle Diseases; Cross-Over Studies; Dinoprostone; Exudates and Transudates; Hydroxyeicosatetraenoic Acids; Inflammation; Male; Proteins; Time Factors; Zymosan

The role of nitric oxide in lipoxygenase metabolism after a process of ischemia-reperfusion in pancreas transplantation has been evaluated in this study. Sprague-Dawley rats were randomized into three groups, as follows: Group I--Control animals not surgically manipulated; Group II.--Pancreas transplantation, after 12 h of organ preservation; Group III.--Same as II but with administration of NG-nitro-L-arginine methyl esther (a nitric oxide synthase inhibitor) (10 mg/Kg) prior to organ revascularization. The results show post-transplantation increases in leukotriene B4 and 12-hydroxyeicosatraenoic acid levels in pancreatic tissue. Nitric oxide synthase inhibition reversed the increases in 12-hydroxyeicosatetraenoic acid, but was unable to modify leukotriene B4 increases suggesting the existence of a direct effect of nitric oxide on the 12-lipoxygenase metabolism in pancreas transplantation.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Animals; Arachidonate 12-Lipoxygenase; Enzyme Activation; Enzyme Inhibitors; Free Radicals; Gene Expression Regulation; Ischemia; Leukotriene B4; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Organ Preservation; Pancreas; Pancreas Transplantation; Pancreatitis; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The role of nitric oxide in eicosanoid and oxygen-free radical production in the early stages of sodium taurocholate-induced acute necrotizing pancreatitis has been studied. Male Wistar rats were divided into three groups: group I: control group, a volume of 0.1 ml/100 g body wt saline solution was injected at low pressure in the pancreatic duct; group II: acute pancreatitis was induced by administration of 3.5% sodium taurocholate; and group III: intravenous administration of NG-nitro-L-arginine methyl esther (a nitric oxide synthase inhibitor) 5 min before induction of acute pancreatitis as stated for group II. At 5 and 60 min after induction of pancreatitis, blood and pancreas tissue samples were taken for assays. Increases in 6-keto PGF1 alpha, TXB2, PGE2, PGF2 alpha, and 12-HETE were observed in the pancreatic tissue. Lipoperoxidation was also enhanced and remained unaltered after nitric oxide inhibition. The fact that nitric oxide synthase inhibition could only reverse the increases in 6-keto PGF1 alpha and TXB2 levels indicates that in acute pancreatitis endothelial and platelet eicosanoid generation is mediated through an nitric oxide-dependent mechanism. In contrast, nitric oxide appears to be not related with oxygen free radical damage associated with acute pancreatitis.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Animals; Arachidonic Acid; Arginine; Blood Platelets; Endothelium, Vascular; Hydroxyeicosatetraenoic Acids; Lipase; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Organ Size; Pancreas; Pancreatitis; Phospholipases A; Prostaglandins; Rats; Rats, Wistar; Reactive Oxygen Species; Taurocholic Acid; Thromboxane B2

The biochemical changes underlying the clinical manifestations of psoriasis are unknown. Certain chemotactic eicosanoids derived from arachidonic acid metabolism have been suggested to play important roles in psoriasis, because of their presence in lesional psoriatic skin and their ability to elicit skin inflammation and to stimulate epidermal proliferation. The purpose of the present study was to elucidate which eicosanoids might be involved in the early phases of the inflammatory processes of psoriasis. Eicosanoids were analyzed in scale and in lesional skin without scale both in acute guttate and chronic plaque psoriatic lesions. Methods for identification of eicosanoids included reversed-phase high-performance liquid chromatography combined with radioimmunoassay. Leukotriene B4 was present in both acute guttate and chronic plaque skin lesions in biologically active amounts (acute guttate lesions: 18.7 +/- 7.1 ng/g wet tissue in scale and 3.2 +/- 1.5 ng/g wet tissue in lesional skin without scale; chronic plaque lesions: 33.1 +/- 9.7 ng/g wet tissue in scale and 5.3 +/- 2.0 ng/g wet tissue in lesional skin without scale). 12- and 15-hydroxy-eicosatetraenoic acid (HETE) reached biologically active concentrations only in scale of chronic plaque lesions (1,512 +/- 282 and 1,441 +/- 411 ng/g wet tissue, respectively). The level of prostaglandin E2 in chronic plaque lesions was similar to the level in normal skin, while the level in acute guttate lesions was increased twofold (71.0 +/- 14.8 ng/g wet tissue). These results demonstrate that leukotriene B4, but not 12-HETE, is present in acute guttate psoriatic skin lesions in concentrations able to exert biologic effects. Leukotriene B4 may therefore participate in inflammatory changes of acute psoriasis.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Chromatography, High Pressure Liquid; Chronic Disease; Dinoprostone; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Psoriasis; Radioimmunoassay; Skin

Macrophages isolated from liver granulomas of mice infected with Schistosoma mansoni for 8 or 20 wk synthesize predominantly thromboxane A2 with smaller amounts of the PGE2 and PGI2. There is no physiologic production of leukotrienes, as determined by RIA and HPLC. Thromboxane A2 is the predominant arachidonic acid metabolite whether the cells are stimulated by a phagocytic stimuli such as zymosan or the exogenous substrates arachidonic acid and PGH2. These data indicate that the predominant arachidonate enzymatic activity in these cells is thromboxane synthase.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Animals; Arachidonic Acid; Arachidonic Acids; Chronic Disease; Granuloma; Hydroxyeicosatetraenoic Acids; Liver Diseases; Macrophage Activation; Macrophages; Mice; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins H; Schistosomiasis mansoni; SRS-A; Thromboxane A2; Thromboxane-A Synthase