| 1. |
- Fäldt, Jenny, 1971, et al.
(författare)
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Activation of human neutrophils by mycobacterial phenolic glycolipids.
- 1999
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Ingår i: Clinical and experimental immunology. - 0009-9104. ; 118:2, s. 253-60
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between mycobacterial phenolic glycolipids (PGLs) and phagocytes was studied. Human neutrophils were allowed to interact with each of four purified mycobacterial PGLs and the neutrophil production of reactive oxygen metabolites was followed kinetically by luminol-/isoluminol-amplified chemiluminescence. The PGLs from Mycobacterium tuberculosis and Mycobacterium kansasii, respectively, were shown to stimulate the production of oxygen metabolites, while PGLs from Mycobacterium marinum and Mycobacterium bovis BCG, respectively, were unable to induce an oxidative response. Periodate treatment of the M. tuberculosis PGL decreased the production of oxygen radicals, showing the importance of the PGL carbohydrate moiety for the interaction. The activation, however, could not be inhibited by rhamnose or fucose, indicating a complex interaction which probably involves more than one saccharide unit. This is in line with the fact that the activating PGLs from M. tuberculosis and M. kansasii contain tri- and tetrasaccharides, respectively, while the nonactivating PGLs from M. marinum and M. bovis BCG each contain a monosaccharide. The complement receptor 3 (CR3) has earlier been shown to be of importance for the phagocyte binding of mycobacteria, but did not appear to be involved in the activation of neutrophils by PGLs. The subcellular localization of the reactive oxygen metabolites formed was related to the way in which the glycolipids were presented to the cells.
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| 2. |
- Fäldt, Jenny, 1971, et al.
(författare)
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Priming of human neutrophils by mycobacterial lipoarabinomannans: role of granule mobilisation.
- 2001
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Ingår i: Microbes and infection. - 1286-4579. ; 3:13, s. 1101-9
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Tidskriftsartikel (refereegranskat)abstract
- Lipoarabinomannans (LAMs) from mycobacteria were investigated concerning their effect on human neutrophils. Two types of LAM, the mannose-capped ManLAM from the virulent Mycobacterium tuberculosis H37Rv and the mannose-lacking AraLAM from a rapidly growing mycobacterial strain were used. Neither AraLAM nor ManLAM induced any significant direct activation of the NADPH-oxidase. Both LAMs, however, primed the neutrophils so that subsequent stimulation with the peptide chemoattractants fMet-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val-DMet (WKYMVm) and the mammalian lactose-binding lectin galectin-3 resulted in a markedly enhanced oxidative response. The LAM-induced priming was accompanied by an increased exposure of complement receptors 1 and 3 as well as the formyl peptide receptor on the neutrophil surface, suggesting that the enhanced oxidative response could be due to upregulation of receptors on the cell surface as a result of granule mobilisation. Since LAM-primed neutrophils released 65% of the cell content of gelatinase but showed no increased release of vitamin B(12)-binding protein, mobilisation of the gelatinase granules rather than the specific granules is concluded to be responsible for the priming effects. This is in agreement with the subcellular localisation of receptors for fMLF, WKYMVm, as well as galectin-3, which are stored in the secretory vesicles and gelatinase granules. The priming effect appeared very similar to that of Escherichia coli lipopolysaccharide, and since no differences in activity could be detected between AraLAM and ManLAM, we hypothesize that the lipid anchor of the LAM is responsible for the priming effects.
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| 3. |
- Fäldt, Jenny, 1971, et al.
(författare)
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The phagocyte chemiluminescence paradox: luminol can act as an inhibitor of neutrophil NADPH-oxidase activity.
- 1999
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Ingår i: Luminescence : the journal of biological and chemical luminescence. - 1522-7235. ; 14:3, s. 153-60
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Tidskriftsartikel (refereegranskat)abstract
- The chemiluminescence system amplified by luminol or isoluminol is a sensitive and widely used method for determination of respiratory burst products generated by the NADPH-oxidase in phagocytes. The present study shows that luminol, but not isoluminol, can inhibit the release of oxygen metabolites generated by human neutrophil NADPH-oxidase. The difference in structure between luminol and isoluminol (rendering luminol more lipophilic than isoluminol, and thereby membrane-permeable), is suggested to determine indirectly whether or not the molecule is inhibitory. Luminol was shown to have an increased inhibitory effect after preincubation of neutrophils on a surface of aggregated IgG, suggesting that the cells can be transferred from a 'luminol-insensitive' to a 'luminol-sensitive' state. Since luminol had no inhibitory effect in a cell-free NADPH-oxidase system, it is likely that it interferes with the signal transduction pathway, leading to assembly and/or activation of the oxidase. As a consequence of the present results, showing that luminol but not isoluminol can inhibit NADPH-oxidase activity, we suggest that isoluminol is used in future studies of superoxide anion release from phagocytes.
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