Plasma and urinary leukotrienes in sickle cell disease: possible role in the inflammatory process

Ibe, Basil O.; Kurantsin‐Mills, Joseph; Raj, J. Usha; Lessin, Lawrence S.

doi:10.1111/j.1365-2362.1994.tb02060.x

Cited by 23 publications

(12 citation statements)

References 30 publications

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“…For example, net loss of GSH may arise because of increased excretion of GSH adducts as mercapto products (8) or via increased biliary excretion (6). Additionally, urinary excretion of cysteinyl-leukotrienes is reported to be increased in SCD (20). Leukotrienes are biologically potent eicosanoids that are derived from arachidionic acid and have significant roles in the modulation of the inflammatory process, cell adhesiveness, and vascular tone in SCD (38).…”

Section: Discussionmentioning

confidence: 99%

“…Isolation of erythrocyte GSH and measurement of its concentration were performed using a Hewlett-Packard 1100 HPLC system (Hewlett-Packard, Avondale, PA) equipped with a reverse-phase ODS Hypersil column (5 m, 4.6 ϫ 200 mm; Agilent Technologies, Wilmington, DE) and fluorescence detector (model HP 1046A; Hewlett-Packard) as previously described by us (3,20,26,28). Elution of the GSH was accomplished with a 3-13.5% acetonitrile linear gradient in 1% acetic acid (pH 4.25) at a flow rate of 1.1 ml/min.…”

Section: Sample Analysesmentioning

confidence: 99%

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In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell disease

Reid

Badaloo²,

Forrester³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Reid, Marvin, Asha Badaloo, Terrence Forrester, and Farook Jahoor. In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell disease. Am J Physiol Endocrinol Metab 291: E73-E79, 2006. First published January 24, 2006 doi:10.1152/ajpendo.00287.2005.-Despite reports of lower GSH concentration in sickle cell disease (SCD), the in vivo kinetic mechanism(s) responsible for GSH deficiency is unknown. To determine whether suppressed synthesis was responsible for the lower erythrocyte GSH concentration, we used a primed intermittent infusion of [ 2 H2]glycine to measure erythrocyte GSH synthesis in vivo in 23 individuals with homozygous ␤ s SCD and 8 healthy controls. Erythrocyte cysteine concentration, the rate-limiting precursor for GSH synthesis, plasma markers of oxidant damage, and dietary intakes of energy and protein were also measured. Compared with values of controls, SCD subjects had significantly lower erythrocyte GSH (P Ͻ 0.04) and cysteine concentrations (P Ͻ 0.004) but significantly faster fractional rates of GSH synthesis (P Ͻ 0.02). The absolute rates of GSH synthesis in SCD subjects compared with control subjects was greater by ϳ57% (P ϭ 0.062). However, the concentrations of markers of oxidative damage, plasma derivatives of reactive oxygen metabolites, plasma nitrotyrosine, urinary isoprostane-to-creatinine ratio, and GSH-to-GSSG ratio, as well as dietary intakes of energy, protein, and GSH precursor amino acids, were not different between SCD subjects and controls. The findings of this study suggest that the lower erythrocyte GSH of SCD patients is not due to suppressed synthesis or impaired regeneration but rather to increased consumption. In addition, the lower erythrocyte cysteine concentration plus the faster rate of GSH synthesis strongly suggest that the endogenous cysteine supply is not sufficient to meet all anabolic demands; hence, cysteine may be a conditionally essential amino acid in individuals with SCD.

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Section: Discussionmentioning

confidence: 99%

Section: Sample Analysesmentioning

confidence: 99%

In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell disease

Reid

Badaloo²,

Forrester³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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“…15,19 The ELISA kits were purchased from Neogen (Louisville, KY). Curve fitting of the standard and calculation of the amount of metabolite were performed with a weighted nonlinear ELISA program.…”

Section: Sample Collectionmentioning

confidence: 99%

“…[10][11][12] Some lung complications in SCD result from direct or indirect effects of pulmonary microvascular occlusion by sickled erythrocytes and their adhesion to the vascular endothelium, 13,14 leading to release of potent vasoactive molecules, including prostacyclin, thromboxane A 2 , and LTC 4 . 15,16 Indeed, the initiation, progression, and resolution of vaso-occlusive pain episodes due to red blood cell sickling and adhesion to endothelium in the affected tissues have been characterized as "reperfusion injury." 17 Homozygous hemoglobin SS (HbSS) disease patients in steady state have higher circulating thromboxane B 2 and LTC 4 than do control (HbAA) individuals, suggesting a greater expression and activity of LTC 4 synthase.…”

Section: Introductionmentioning

confidence: 99%

Sickle Erythrocytes and Platelets Augment Lung Leukotriene Synthesis with Downregulation of Anti‐Inflammatory Proteins: Relevance in the Pathology of the Acute Chest Syndrome

et al. 2014

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Initiation, progression, and resolution of vaso-occlusive pain episodes in sickle cell disease (SCD) have been recognized as reperfusion injury, which provokes an inflammatory response in the pulmonary circulation. Some 5-lipoxygenase (5-lox) metabolites are potent vasoconstrictors in the pulmonary circulation. We studied stimulation of production of the inflammatory eicosanoids leukotrienes (LTs) and prostaglandin E 2 (PGE 2 ) by isolated rat lungs perfused with sickle (HbSS) erythrocytes. Our hypothesis is that HbSS erythrocytes produce more LTs than normal (HbAA) erythrocytes, which can induce vaso-occlusive episodes in SCD patients. Lung perfusates were collected at specific time points and purified by high-pressure liquid chromatography, and LTC 4 and PGE 2 contents were measured by enzyme-linked immunosorbent assay (ELISA). Rat lung explants were also cultured with purified HbAA and HbSS peptides, and 5-lox, cyclooxygenase 1/2, and platelet-activating factor receptor (PAFR) proteins were measured by Western blotting, while prostacyclin and LTs produced by cultured lung explants were measured by ELISA. Lung weight gain and blood gas data were not different among the groups. HbSS-perfused lungs produced more LTC 4 and PGE 2 than HbAA-perfused lungs: 10.40 AE 0.62 versus 0.92 AE 0.2 ng/g dry lung weight (mean AE SEM; P ¼ 0.0001) for LTC 4 . Inclusion of autologous platelets (platelet-rich plasma) elevated LTC 4 production to 12.6 AE 0.96 and 7 AE 0.60 ng/g dry lung weight in HbSS and HbAA perfusates, respectively. HbSS lungs also expressed more 5-lox and PAFR. The data suggest that HbSS erythrocytes and activated platelets in patient's pulmonary microcirculation will enhance the synthesis and release of the proinflammatory mediators LTC 4 and PGE 2 , both of which may contribute to onset of the acute chest syndrome in SCD.

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“…Hydrolysis of this intermediate forms LTB 4 , a potent leukocyte chemoattractant that also displays leukocyte activating functions (17). Regarding hemolysis-related inflammatory conditions, it has been shown that increased LT concentrations are found in plasma and urine of SCD patients at steady state (18,19), and that plasma levels of LTB 4 are further increased during vasoocclusion and acute chest syndrome episodes (20).…”

mentioning

confidence: 99%

Leukotriene B4 Mediates Neutrophil Migration Induced by Heme

Monteiro

Pinheiro

Luna-Gomes

et al. 2011

The Journal of Immunology

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High concentrations of free heme found during hemolytic events or cell damage leads to inflammation, characterized by neutrophil recruitment and production of reactive oxygen species, through mechanisms not yet elucidated. In this study, we provide evidence that heme-induced neutrophilic inflammation depends on endogenous activity of the macrophage-derived lipid mediator leukotriene B4 (LTB4). In vivo, heme-induced neutrophil recruitment into the peritoneal cavity of mice was attenuated by pretreatment with 5-lipoxygenase (5-LO) inhibitors and leukotriene B4 receptor 1 (BLT1) receptor antagonists as well as in 5-LO knockout (5-LO−/−) mice. Heme administration in vivo increased peritoneal levels of LTB4 prior to and during neutrophil recruitment. Evidence that LTB4 was synthesized by resident macrophages, but not mast cells, included the following: 1) immuno-localization of heme-induced LTB4 was compartmentalized exclusively within lipid bodies of resident macrophages; 2) an increase in the macrophage population enhanced heme-induced neutrophil migration; 3) depletion of resident mast cells did not affect heme-induced LTB4 production or neutrophil influx; 4) increased levels of LTB4 were found in heme-stimulated peritoneal cavities displaying increased macrophage numbers; and 5) in vitro, heme was able to activate directly macrophages to synthesize LTB4. Our findings uncover a crucial role of LTB4 in neutrophil migration induced by heme and suggest that beneficial therapeutic outcomes could be achieved by targeting the 5-LO pathway in the treatment of inflammation associated with hemolytic processes.

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Plasma and urinary leukotrienes in sickle cell disease: possible role in the inflammatory process

Cited by 23 publications

References 30 publications

In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell disease

In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell disease

Sickle Erythrocytes and Platelets Augment Lung Leukotriene Synthesis with Downregulation of Anti‐Inflammatory Proteins: Relevance in the Pathology of the Acute Chest Syndrome

Leukotriene B4 Mediates Neutrophil Migration Induced by Heme

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