| 1. |
- Almkvist, Jenny, 1971, et al.
(författare)
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Activation of the neutrophil nicotinamide adenine dinucleotide phosphate oxidase by galectin-1.
- 2002
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 168:8, s. 4034-4041
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Tidskriftsartikel (refereegranskat)abstract
- Galectins are a group of lactose-binding proteins widely distributed in nature. Twelve mammalian galectins have so far been identified, but their functions are to a large extent unknown. In this work we study galectin-1 in its interaction with human neutrophils, with regard to both cell surface binding and activation of the superoxide-producing NADPH-oxidase. We show that galectin-1 is able to activate the neutrophil NADPH-oxidase, provided that the cells have been primed by extravasation from the blood into the tissue, an activation pattern that is similar to that of galectin-3. Using in vitro priming protocols, the galectin-1 responsiveness was found to correlate to granule mobilization and galectin-1 binding to the cells, suggesting the presence of granule-localized receptors that are up-regulated to the cell surface upon priming. By galectin-1 overlay of fractionated neutrophils we identified potential galectin-1 receptor candidates localized in the membranes of the secretory vesicle and gelatinase granules. The binding of galectin-1 and galectin-3 to neutrophil proteins was compared, as were the dose dependencies for activation by the two lectins. The results suggest that, although similarities are found between the two galectins, they appear to activate the NADPH-oxidase using different receptors. In conclusion, galectin-1 appears to have proinflammatory functions, mediated through activation of the neutrophil respiratory burst.
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| 2. |
- Almkvist, Jenny, 1971, et al.
(författare)
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Lipopolysaccharide-induced gelatinase granule mobilization primes neutrophils for activation by galectin-3 and formylmethionyl-Leu-Phe.
- 2001
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Ingår i: Infection and immunity. - 0019-9567 .- 1098-5522. ; 69:2, s. 832-7
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Tidskriftsartikel (refereegranskat)abstract
- We have earlier shown that galectin-3, a lactose-binding mammalian lectin that is secreted from activated macrophages, basophils, and mast cells, induces activation of the NADPH oxidase in exudated but not in peripheral blood neutrophils (A. Karlsson, P. Follin, H. Leffler, and C. Dahlgren, Blood 91:3430-3438, 1998). The alteration in responsiveness occurring during extravasation correlated with mobilization of the gelatinase and/or specific granules to the cell surface, indicating a role for mobilizable galectin-3 receptors. In this study we have investigated galectin-3-induced NADPH oxidase activation, measured as superoxide production, in lipopolysaccharide (LPS)-primed neutrophils. Upon galectin-3 challenge, the LPS-primed cells produced superoxide, both extracellularly and intracellularly. A primed extracellular response to formylmethionyl-Leu-Phe (fMLF) was also achieved. The exposure of complement receptors 1 and 3 as well as the formyl peptide receptor on the cell surface was markedly increased after LPS treatment, indicating that granule fusion with the plasma membrane had occurred. Further assessment of specific markers for neutrophil granules showed that the LPS treatment had mobilized the gelatinase granules but only a minor fraction of the specific granules. We thus suggest that the mechanism behind LPS priming lies at the level of granule (receptor) mobilization for galectin-3 as well as for fMLF.
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| 3. |
- Almkvist, Jenny, 1971, et al.
(författare)
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Newcastle disease virus neuraminidase primes neutrophils for stimulation by galectin-3 and formyl-Met-Leu-Phe
- 2004
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Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 298:1, s. 74-82
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Tidskriftsartikel (refereegranskat)abstract
- Human neutrophils are activated by the beta-galactoside-binding lectin galectin-3, provided that the cells are primed by in vivo extravasation or by in vitro preactivation with, for example, LPS. Removal of terminal sialic acid can change neutrophil functionality and responsiveness due to exposure of underlying glycoconjugate receptors or change in surface charge. Here, we investigated whether such alteration of the cell surface carbohydrate composition can alter the responsiveness of the cells to galectin-3. Neutrophils were treated with neuraminidases (NA) of different origins: Clostridium perfringens (CP), Salmonella typhimurium, Vibrio cholerae, and Newcastle disease virus (NDV). In the presence of NDV-NA, but no other NA, the otherwise non-responding neutrophils responded readily to galectin-3 by activation of the NADPH-oxidase. The galectin-3 priming effect was inhibited by the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetyl-neuraminic acid. Earlier studies have shown that priming of the neutrophil response to galectin-3 with, for example, LPS is paralleled by degranulation of intracellular vesicles and granules and upregulation of potential galectin-3 receptors. Also, NDV-NA (but not CP-NA) treatment induced degranulation, shown as an upregulation of complement receptor 3. Since not only the galectin response but also the response to the chemoattractant fMLF was primed, NDV-NA appears to induce a general priming phenomenon, possibly due to receptor upregulation by degranulation.
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| 4. |
- Bergh Thorén, Fredrik, 1976, et al.
(författare)
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A hepatitis C virus-encoded, nonstructural protein (NS3) triggers dysfunction and apoptosis in lymphocytes: role of NADPH oxidase-derived oxygen radicals
- 2004
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Ingår i: Journal of leukocyte biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 76:6, s. 1180-6
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Tidskriftsartikel (refereegranskat)abstract
- The persistent infection caused by hepatitis C virus (HCV) is presumably explained by a deficient immune response to the infection, but the basis for the inefficiency of immune-mediated virus eradication is not known in detail. This study addresses mechanisms of relevance to dysfunction of cytotoxic lymphocytes in HCV infection, with a focus on the role of phagocyte-derived oxygen radicals. We show that NS3, a nonstructural, HCV-encoded protein, induces a prolonged release of oxygen radicals from mononuclear and polymorphnuclear phagocytes by activating a key enzyme in radical formation, the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The NS3-activated phagocytes, in turn, induced dysfunction and/or apoptosis in three major subsets of lymphocytes of relevance to defense against HCV infection: CD3+/56- T cells, CD3-/56+ natural killer (NK) cells, and CD3+/56+ NKT cells. Two inhibitors of the NADPH oxidase, histamine and diphenylene iodonium, suppressed the NS3-induced oxygen radical production and efficiently protected lymphocytes against NS3-induced apoptosis and dysfunction. In conclusion, we propose that NS3, by triggering oxygen radical formation in phagocytes, may contribute to the dysfunction of antiviral lymphocytes in HCV-infected liver tissue and that strategies to circumvent oxidative stress may be useful in preventing HCV-associated carcinogenesis and facilitating lymphocyte-mediated clearance of infected cells.
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| 5. |
- Betten, Åsa, 1967, et al.
(författare)
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A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis
- 2001
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Ingår i: J Clin Invest. ; 108:8, s. 1221-8
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Tidskriftsartikel (refereegranskat)abstract
- Infection with Helicobacter pylori causes chronic gastritis, which is characterized by a dense mucosal infiltration by inflammatory cells such as monocytes/macrophages. H. pylori-induced inflammation is a risk factor for the development of gastric adenocarcinoma, but the mechanisms involved in H. pylori-associated carcinogenesis are poorly understood. A cecropin-like H. pylori peptide, Hp(2-20), was found to be a monocyte chemoattractant and activated the monocyte NADPH-oxidase to produce oxygen radicals. The receptors mediating monocyte activation were identified as FPRL1 and the monocyte-specific orphan receptor FPRL2. Hp(2-20)-activated monocytes inhibited lymphocytes with antitumor properties, such as CD56+ natural killer (NK) cells and CD3epsilon+ T cells. The changes observed in NK cells and T cells--a reduced antitumor cytotoxicity, downregulation of CD3zeta expression, and apoptosis--were mediated by Hp(2-20)-induced oxygen radicals. Histamine, a gastric mucosal constituent, rescued NK cells and T cells from inhibition and apoptosis by suppressing Hp(2-20)-induced oxygen radical formation. We conclude that H. pylori expression of this monocyte-activating peptide contributes to its ability to attract and activate monocytes and reduces the function and viability of antineoplastic lymphocytes. These novel mechanisms may be subject to local, histaminergic regulation in the gastric mucosa.
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| 6. |
- Betten, Åsa, 1967, et al.
(författare)
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Histamine inhibits neutrophil NADPH oxidase activity triggered by the lipoxin A4 receptor-specific peptide agonist Trp-Lys-Tyr-Met-Val-Met
- 2003
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Ingår i: Scand J Immunol. ; 58:3, s. 321-6
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Tidskriftsartikel (refereegranskat)abstract
- The vasoactive amine histamine is found at high concentrations in the immune and inflammatory tissues. Earlier studies have revealed that histamine regulates the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent formation of oxygen radicals by phagocytic cells. However, the effects of histamine on intracellular signal transduction mechanisms of relevance to oxidase regulation remain controversial. For this study, we investigated the effects of histamine on NADPH oxidase activity in human neutrophil granulocytes triggered by a lipoxin A4 receptor agonist [the hexapeptide Trp-Lys-Tyr-Met-Val-Met (WKYMVM), a formyl peptide receptor (FPR) agonist (the chemotactic tripeptide formylmethionyl-leucyl-phenylalanine (fMLF)) and an activator of protein kinase C (phorbol myristate acetate (PMA)]. We report that histamine, acting via H2-type histamine receptors (H2R), suppresses NADPH oxidase-dependent formation of oxygen radicals induced by WKYMVM and fMLF but not that induced by PMA. Peptide-induced mobilization of granule-localized complement receptor 3 (CR3) was unaffected by histamine suggesting that the inhibition specifically affected NADPH oxidase activation. Our data suggest that histamine downregulates FPRL1- and FPR-induced NADPH oxidase activity upstream of protein kinase C (PKC) and downstream of the separation of the peptide-induced signal into granule secretion and oxidase activation.
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| 7. |
- Betten, Åsa, 1967, et al.
(författare)
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Oxygen radical-induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin
- 2004
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Ingår i: J Leukoc Biol. ; 75:6, s. 1111-5
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells are functionally suppressed and induced to apoptosis by reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs). These inhibitory events are reversed by the biogenic amine serotonin. MPs generate hydrogen peroxide (H(2)O(2)), which is processed further by myeloperoxidase (MPO) to even more toxic compounds. Earlier studies suggest that serotonin scavenges MP-derived oxygen radicals generated by the MPO-H(2)O(2) system. These findings led us to explore the capability of MPO-deficient MPs to induce NK cell dysfunction. We show that MPs recovered from subjects with MPO deficiency trigger inhibition of NK cells. In addition, MPs recovered from healthy subjects conveyed suppression of NK cells in the presence of the MPO inhibitor ceruloplasmin. We conclude that ROS-dependent inhibition of NK cell function is unrestricted by the availability of MPO-derived oxygen radicals and that the protecting properties of serotonin may operate in the absence of functional MPO. Our data suggest a complex mechanism of MP-induced NK cell inhibition, which comprises the generation of interchangeable oxygen radicals.
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| 8. |
- Bylund, Johan, 1975, et al.
(författare)
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Cytochalasin B triggers a novel pertussis toxin sensitive pathway in TNF-alpha primed neutrophils
- 2004
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Ingår i: BMC cell biology. - 1471-2121. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cytochalasin B does not directly activate the oxygen-radical-producing NADPH oxidase activity of neutrophils but transfers desensitized G-protein coupled receptors (GPCR) into an active signaling state by uncoupling GCPR from the cytoskeleton. The receptor uncoupling results in respiratory burst activity when signals generated by reactivated formyl peptide receptors trigger the NADPH-oxidase to produce superoxide anions. RESULTS: Tumor necrosis factor alpha (TNF-alpha) primes neutrophils for subsequent activation by cytochalasin B. Pretreatment with TNF-alpha induced mobilization of receptor-storing neutrophil organelles, suggesting that receptor up-regulation significantly contributes to the response, but the receptor mobilization was not sufficient for induction of the cytochalasin B sensitive state. The TNF-alpha primed state resembled that of the desensitized non-signaling state of agonist-occupied neutrophil formyl peptide receptors. The fact that the TNF-alpha primed, cytochalasin B-triggered activation process was pertussis toxin sensitive suggests that the activation process involves a GPCR. Based on desensitization experiments the unidentified receptor was found to be distinct from the C5a receptor as well as the formyl peptide receptor family members FPR and FPRL1. Based on the fact the occupied and desensitized receptors for interleukin-8 and platelet activating factor could not be reactivated by cytochalasin B, also these could be excluded as receptor candidates involved in the TNF-alpha primed state. CONCLUSIONS: The TNF-alpha-induced priming signals could possibly trigger a release of an endogenous GPCR-agonist, amplifying the response to the receptor-uncoupling effect of cytochalasin B. However, no such substance could be found, suggesting that TNF-alpha can transfer G-protein coupled receptors to a signaling state independently of agonist binding.
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| 9. |
- Bylund, Johan, 1975, et al.
(författare)
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Lipopolysaccharide-induced granule mobilization and priming of the neutrophil response to Helicobacter pylori peptide Hp(2-20), which activates formyl peptide receptor-like 1
- 2002
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Ingår i: Infect Immun. ; 70:6, s. 2908-14
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Tidskriftsartikel (refereegranskat)abstract
- The cecropin-like bactericidal peptide Hp(2-20) from Helicobacter pylori induces activation of the NADPH oxidase in human neutrophils via formyl peptide receptor-like 1 (FPRL1) (J. Bylund, T. Christophe, F. Boulay, T. Nystrom, A. Karlsson, and C. Dahlgren, Antimicrob. Agents Chemother. 45:1700-1704, 2001). Here we investigated the ability of bacterial lipopolysaccharide (LPS) to prime this response. Neutrophils treated with LPS for 30 min at 37 degrees C produced substantially more superoxide anion than control cells upon stimulation with Hp(2-20). Hence, LPS primed the cells for subsequent stimulation through FPRL1. To study the molecular background of this priming phenomenon, we measured the degrees of granule mobilization and concomitant receptor upregulation to the cell surface in LPS-treated cells. Exposure of complement receptors 1 and 3 as well as the formyl peptide receptor (FPR) was markedly increased after LPS treatment. Since approximately 60% of the gelatinase granules were mobilized while the specific granules were retained, we hypothesized that the gelatinase granules were potential stores of FPRL1. The presence of FPRL1 mainly in the gelatinase granules was confirmed by Western blotting of subcellular fractions of resting neutrophils. These results suggest that the mechanism behind the LPS-induced priming of FPRL1-mediated responses lies at the level of granule (receptor) mobilization.
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| 10. |
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