Arachidonic acid metabolism by human monocytes. Studies with platelet-depleted cultures.

Pawlowski, Nicholas A.; Kaplan, Gilla; Hamill, Anne L.; Cohn, Zanvil A.; Scott, William

doi:10.1084/jem.158.2.393

Cited by 221 publications

(69 citation statements)

References 43 publications

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“…In monocytes, the soluble stimulus calcium ionophore A23187 primarily induced the release of 5-1ipoxygenase arachidonate products (89.5% of total eicosanoids assayed), in agreement with previous studies (35)(36)(37)(38). LTB4 was the major product of calcium ionophore A23187-stimulated monocytes, with a ratio of TXBjPGE2/LTB4/LTC4 of 6:1:54:7 observed.…”

Section: Discussionsupporting

confidence: 91%

Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.

Yong

Emil

Henderson

1994

The Journal of Experimental Medicine

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SummaryToxoflasma gondii tachyzoites markedly alter the profile of eicosanoids released by human mononuclear phagocytes. Freshly isolated, 2-h adherent human monocytes release both cyclooxygenase (e.g., thromboxane [TX] B2, prostaglandin [PG] E2) and 5-1ipoxygenase (e.g., leukotriene [LT] ]]4, LTC4) products of arachidonic acid metabolism after stimulation by the calcium ionophore A23187 or ingestion of opsonized zymosan particles or heat-killed T. gondii. However, after incubation with viable T. gondii, normal and chronic granulomatous disease monocytes release only the cyclooxygenase products TXB2 and PGE2 and fail to form LTB4, LTC4, or other 5-1ipoxy-genase products. Monocytes maintained in culture for 5 d lose this capacity to release TXB2 and PGE2 after incubation with T. gondii. T. gondii significantly inhibit calcium ionophore A23187-induced LTB4 release by monocyte-derived macrophages; heat-killed organisms do not affect this calcium ionophore A23187-induced release of LTB4. T. gondii-induced inhibition of LTB4 release by calcium ionophore A23187-stimulated monocyte-derived macrophages is reversed by interferon (IFN)-3' treatment of the monolayers. LTB4 induced extensive damage to the cellular membranes and cytoplasmic contents of the organisms as observed by transmission electron microscopy. Exogenous LTB4 (10-6 M) induced intracellular killing of ingested T. gondii by non-IFN-q,-treated monocyte-derived macrophages. IFN-y-induced antitoxoplasma activity in monocyte-derived macrophages was inhibited by the selective 5-1ipoxygenase inhibitor zileuton but not by the cyclooxygenase inhibitor indomethacin. These findings suggest a novel role for 5-1ipoxygenase arachidonic acid products in human macrophage IFN-3,-induced antitoxoplasma activity.H uman monocytes, but not monocyte-derived macrophages, are cytotoxic to Toxoplasma gondii, an obligate intracellular protozoal parasite (1-3). Monocytes possess a granule peroxidase identical to myeloperoxidase (MPO) 1 of neutrophils and respond to stimulation with a respiratory burst leading to the formation of superoxide anion (Of) and hydrogen peroxide (H202) (4). Monocytes derived from peripheral blood and maintained as adherent cells in culture undergo a variety of biochemical and morphologic changes and differentiate into cells resembling tissue macrophages (5-7). During this transformation in culture, there is a progressive loss of the granule peroxidase (5, 8); after an initial rise at day 3, H202 release also greatly decreases (9). Treatment of 1 Abbreviations used in this paper: CGD, chronic granulomatous disease; HETE, hydroxyeicosatetraenoic acid; IFA, indirect fluorescence antibody; LT, leukotriene; MPO, myeloperoxidase; TX, thromboxane. monocyte-derived macrophages with IFN-3, results in their activation with a concomitant increase in H202 generation when stimulated (7,10).The capacity to generate oxygen radicals and the presence of MPO has been correlated with the antiprotozoal activity of phagocytes (2,11,12). Neutrophils and freshly isolated peroxi...

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Section: Discussionsupporting

confidence: 91%

Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.

Yong

Emil

Henderson

1994

The Journal of Experimental Medicine

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“…Human peripheral blood monocytes (PBMos) were isolated from pneumonia patients and healthy volunteers by density-gradient separation. 29 Cell purity was greater than 95% (determined by flow cytometry), and cell viability was greater than 95% (determined by trypan blue exclusion). Lung specimens were obtained by autopsy from 5 pneumonia patients and 5 control patients (4 patients who died of myocardial infarction and 1 patient who died from drug intoxication).…”

Section: Patient Samplesmentioning

confidence: 99%

Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely inflamed lung

Wygrecka¹,

Marsh

Morty

et al. 2009

Blood

175

185

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Cell surface-associated proteolysis plays a crucial role in the migration of mononuclear phagocytes to sites of inflammation. The glycolytic enzyme enolase-1 (ENO-1) binds plasminogen at the cell surface, enhancing local plasmin production. This study addressed the role played by ENO-1 in lipopolysaccharide (LPS)-driven chemokine-directed monocyte migration and matrix invasion in vitro, as well as recruitment of monocytes to the alveolar compartment in vivo. LPS rapidly up-regulated ENO-1 cell-surface expression on human blood monocytes and U937 cells due to protein translocation from cytosolic pools, which increased plasmin generation, enhanced monocyte migration through epithelial monolayers, and promoted matrix degradation. These effects were abrogated by antibodies directed against the plasminogen binding site of ENO-1. Overexpression of ENO-1 in U937 cells increased their migratory and matrix-penetrating capacity, which was suppressed by overexpression of a truncated ENO-1 variant lacking the plasminogen binding site (ENO-1⌬PLG). In vivo, intratracheal LPS application in mice promoted alveolar recruitment of monocytic cells that overexpressed ENO-1, but not of cells overexpressing ENO-1⌬PLG. Consistent with these data, pneumoniapatients exhibited increased ENO-1 cellsurface expression on blood monocytes and intense ENO-1 staining of mononuclear cells in the alveolar space. These data suggest an important mechanism of inflammatory cell invasion mediated by increased cell-surface expression of ENO-1. (Blood. 2009;113:5588-5598) IntroductionMonocytes are circulating mononuclear phagocytes with a broad spectrum of activities and functions. In pathologic conditions associated with acute or chronic inflammation, monocytes migrate into the affected tissues and differentiate into tissue macrophages. 1,2 Thus, monocytes and tissue macrophages are critical cellular components of the host defense system against infectious diseases, including forms of pneumonia, and have important functions in both native and acquired immunity. They are responsible for the phagocytosis and clearance of invading microorganisms, regulate antimicrobial programs of gene expression, are a potent source of inflammatory cytokines, and interact with T cells through cell-cell or cytokine-mediated mechanisms, thereby facilitating acquired immunity to specific pathogens. [1][2][3][4][5][6][7] In atherosclerosis, monocytes infiltrate atherosclerotic plaques, accumulate lipidrich material, and differentiate into macrophage-type foam cells. 8 Moreover, tumor-infiltrating monocytes may play a role in tumor progression and metastasis by different mechanisms, including regulation of angiogenesis. 9 Many of these activities depend upon the ability of monocytes to localize and regulate cell surfaceassociated proteolytic activity.The enzymes of the fibrinolytic system represent one of the most broadly distributed cell surface-associated protease systems. The accumulation of plasminogen (PLG) and its activators, namely urokinase (u-PA) and tissue-plasminog...

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“…37 Purity was Ͼ95% as determined by flow cytometry, and viability was Ͼ95% as determined by trypan blue exclusion. In addition, human myelomonocytic HL-60 cells (German Collection of Microorganisms and Cell Cultures), which were maintained in RPMI medium supplemented with 10% FCS, 1 mmol/L glutamine, 1% sodium pyruvate, 100 U/mL penicillin, and 100 g/mL streptomycin (Gibco-BRL), were used.…”

Section: Isolation Of Leukocytesmentioning

confidence: 99%

Enzymatically Modified, Nonoxidized LDL Induces Selective Adhesion and Transmigration of Monocytes and T-Lymphocytes Through Human Endothelial Cell Monolayers

Klouche

May

Hemmes

et al. 1999

ATVB

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Abstract-Circulating monocytes and T lymphocytes extravasate through the endothelium at sites of developing atheromatous lesions, where they tend to accumulate and mediate the progression of the disease. We have previously demonstrated the presence of an enzymatically degraded, nonoxidized form of LDL (E-LDL) in early human fatty streaks, which possesses major biological properties of an atherogenic lipoprotein. The effects of E-LDL on human endothelial cells have now been studied with respect to adhesion and transmigration of monocytes and T lymphocytes. E-LDL induced a rapid and dose-dependent selective adhesion of monocytes and T lymphocytes to endothelial cell monolayers within 30 minutes of incubation. Maximal increases in the number of adherent monocytes (8-fold) and of adherent T lymphocytes (4-fold) were observed after treatment with 50 g/mL E-LDL. E-LDL was more active than oxidized LDL (ox-LDL), whereas native LDL produced only minor adhesive effects. Both E-LDL and ox-LDL enhanced transmigration of monocytes and of T lymphocytes through endothelial monolayers. Again, E-LDL was more potent than ox-LDL, inducing transmigration to a similar extent as N-formyl-Met-Leu-Phe. In endothelial cells, E-LDL stimulated upregulation of intercellular adhesion molecule-1 (ICAM-1), platelet-endothelial cells adhesion molecule-1 (PECAM-1), P-selectin, and E-selectin with distinct kinetics. Analyses with blocking antibodies indicated that ICAM-1 and P-selectin together mediated approximately 70% of cell adhesion, whereas blocking of PECAM-1 had no effect on adhesion but reduced transmigration to less than 50% of controls. E-LDL also upregulated expression of ICAM-1 in human aortic smooth muscle cells, and this correlated with increased adhesion of T lymphocytes. E-LDL is thus able to promote the selective adhesion of monocytes and T lymphocytes to the endothelium, stimulate transmigration of these cells, and foster their retention in the vessel wall by increasing their adherence to smooth muscle cells. These findings underline the potential significance of E-LDL in the pathogenesis of atherosclerosis.

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Arachidonic acid metabolism by human monocytes. Studies with platelet-depleted cultures.

Cited by 221 publications

References 43 publications

Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.

Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.

Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely inflamed lung

Enzymatically Modified, Nonoxidized LDL Induces Selective Adhesion and Transmigration of Monocytes and T-Lymphocytes Through Human Endothelial Cell Monolayers

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