Disparate gene expression of chemotactic cytokines by human mononuclear phagocytes

Strieter, Robert M.; Chensue, Stephen W.; Standiford, Theodore J.; Basha, Michael A.; Showell, Henry J.; Kunkel, Steven L.

doi:10.1016/0006-291x(90)90893-r

Cited by 58 publications

(19 citation statements)

References 8 publications

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“…Interleukin 8 is a cytokine, produced by monocytes, macrophages, endothelial cells, hepatocytes and other cell-types which has specific chemotactic and activating effects on neutrophils (28). Mononuclear phagocytes express IL8 in response to stimulation with TNFa or IL1 (29) and after phagocytosis (30). It is therefore also possible that the extreme phagocytosis of glycolipids in Gaucher disease triggers the release of IL8 and sCD14.…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of M-CSF, sCD14 and IL8 in Type 1 Gaucher Disease

Hollak

Evers

Aerts

et al. 1997

Blood Cells, Molecules, and Diseases

135

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ABSTRACT:In type 1 Gaucher disease, decreased activity of glucocerebrosidase results in accumulation of glucosylceramide in macrophages. Infiltration of liver, spleen and bone marrow by lipid-laden macrophages leads to hepatosplenomegaly, bone lesions and cytopenia. These abnormal macrophages may produce and release macrophage derived factors and cytokines, which could contribute to the pathophysiology of the disease. Whether these cytokines and factors are elevated in Gaucher disease is currently unknown. In 29 type 1 Gaucher disease patients we measured serum levels of the macrophage derived cytokines IL8, IL6, TNFa , M-CSF and the monocyte/macrophage activation marker sCD14. These factors were studied in relation to disease severity and during treatment with enzyme supplementation therapy. Most patients showed remarkably elevated levels of M-CSF (2-8 fold) and sCD14 (2-5 fold) as compared to normal controls. Levels of IL8 were elevated in all patients (2-20 fold), whereas levels of IL6 and TNFa were normal. There was a significant correlation between severity of the disease as determined by the severity score index (SSI), and M-CSF, sCD14 and IL8 levels. M-CSF and sCD14 levels also correlated with the excess liver and spleen volumes. During treatment with alglucerase, levels of M-CSF and sCD14 declined, but IL8 remained unchanged. The relative reduction in excess liver and spleen volume did not correlate with the relative reduction in M-CSF or sCD14 levels. We conclude that serum levels of M-CSF, sCD14 and IL8 are increased in type 1 Gaucher disease. The biological activities of M-CSF and IL8 may add to the pathophysiology of the disease.

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Section: Discussionmentioning

confidence: 99%

Elevated Levels of M-CSF, sCD14 and IL8 in Type 1 Gaucher Disease

Hollak

Evers

Aerts

et al. 1997

Blood Cells, Molecules, and Diseases

135

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“…It is well known that LPS activates macrophages to release proinflammatory mediators, including superoxide (38), cytokines (39), NO (17), and AA metabolites (40). Short term (2-h) treatment with LPS has been reported to prime PBM for increased AA release and enhanced LT synthesis following stimulation with FMLP (41).…”

Section: Discussionmentioning

confidence: 99%

Prolonged Exposure to Lipopolysaccharide Inhibits Macrophage 5-Lipoxygenase Metabolism Via Induction of Nitric Oxide Synthesis

Coffey

Phare

Peters‐Golden

2000

The Journal of Immunology

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LPS from bacteria can result in the development of sepsis syndrome and acute lung injury. Although acute exposure to endotoxin primes leukocytes for enhanced synthesis of leukotrienes (LT), little is known about the effect of chronic exposure. Therefore, we determined the effect of prolonged LPS treatment on 5-lipoxygenase (5-LO) metabolism of arachidonic acid in alveolar macrophages (AM) and in peripheral blood monocytes. Pretreatment of AM with LPS caused time- and dose-dependent suppression of LT synthetic capacity. LPS pretreatment failed to inhibit arachidonic acid (AA) release. The fact that LPS inhibited LT synthesis from endogenous AA more than from exogenous AA suggested an effect on 5-LO-activating protein (FLAP). In addition, an inhibitory effect of LPS treatment on AM 5-LO activity was suggested by cell-free 5-LO enzyme assay. No effect on the expression of either 5-LO or FLAP proteins was observed. New protein synthesis was necessary for LPS-induced reduction of 5-LO metabolism in AM, and immunoblotting demonstrated marked induction of NO synthase (NOS). Inhibition by LPS was reproduced by an NO donor and was abrogated by inhibitors of constitutive and inducible NOS. Compared with AM, peripheral blood monocytes exhibited no suppression by LPS of 5-LO metabolism and no induction of inducible NOS. We conclude that prolonged exposure to LPS impairs AM 5-LO metabolism by NO-mediated suppression of both 5-LO and FLAP function. Because LT contribute to antimicrobial defense, this down-regulation of 5-LO metabolism may contribute to the increased susceptibility to pneumonia in patients following sepsis.

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“…Put together with the results of previous in vitro studies' 1230~33) , our findings suggest that this effect is mediated through reduction of monocyte activation by adherent activated platelets. It is known that inhibition of monocyte activation not only affects the surface expression of adhesion molecules and procoagulant activity, but also the secretion of cytokines' 38 '. Monocyte-derived cytokines such as interleukin-1/?…”

Section: Discussionmentioning

confidence: 99%

Reduction of monocyte-platelet interaction and monocyte activation in patients receiving antiplatelet therapy after coronary stent implantation

May¹,

Neumann²,

Gawaz³

et al. 1997

European Heart Journal

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Background Monocyte activation induces different procoagulant and proadhesive inflammatory responses and thus may play a role in thrombotic complications after coronary interventions. Monocyte-platelet interaction may trigger these effects inducing monocyte activation.Aims To characterize the effect of antiplatelet vs anticoagulation therapy on monocyte-platelet interaction and monocyte function after intracoronary stenting. Methods and ResultsImmediately before, and during the first 12 days after successful coronary stenting, monocyteplatelet conjugates and monocyte function were assessed by flow cytometric detection of GPIIb/IIIa (CD41) on monocytes and by monocyte surface exposure of Mac-1 (CD1 lb/ CD 18) and L-selectin (CD62L). Twenty patients receiving combined antiplatelet therapy (ticlopidine, aspirin) were compared to 20 patients with standard anticoagulation (phenprocoumon, overlapping heparin, aspirin). Before stenting, monocyte-platelet conjugates and Mac-1 surface expression in both groups were significantly increased, while L-selectin was significantly diminished. Anticoagulation did not change these variables significantly during the subsequent 12 days. In contrast, antiplatelet therapy reduced platelet-monocyte conjugates by 46 ±9-3% (mean ± SEM, Z'=00019) within 4 days, which was associated with a decrease in Mac-1 expression (28 ± 6-7%, />=00013) and an increase in L-selectin (56±150%, P=00061). ConclusionAfter intracoronary stenting, combined antiplatelet therapy, but not anticoagulation, causes reduction of monocyte-platelet interaction, which is associated with monocyte deactivation. This may contribute to a decreased risk for thrombotic events.

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Disparate gene expression of chemotactic cytokines by human mononuclear phagocytes

Cited by 58 publications

References 8 publications

Elevated Levels of M-CSF, sCD14 and IL8 in Type 1 Gaucher Disease

Elevated Levels of M-CSF, sCD14 and IL8 in Type 1 Gaucher Disease

Prolonged Exposure to Lipopolysaccharide Inhibits Macrophage 5-Lipoxygenase Metabolism Via Induction of Nitric Oxide Synthesis

Reduction of monocyte-platelet interaction and monocyte activation in patients receiving antiplatelet therapy after coronary stent implantation

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