| 1. |
- Almkvist, Jenny, 1971, et al.
(författare)
-
Lipopolysaccharide-induced gelatinase granule mobilization primes neutrophils for activation by galectin-3 and formylmethionyl-Leu-Phe.
- 2001
-
Ingår i: Infection and immunity. - 0019-9567 .- 1098-5522. ; 69:2, s. 832-7
-
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.
|
|
| 2. |
- Almkvist, Jenny, 1971, et al.
(författare)
-
Activation of the neutrophil nicotinamide adenine dinucleotide phosphate oxidase by galectin-1.
- 2002
-
Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 168:8, s. 4034-4041
-
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.
|
|
| 3. |
- Almkvist, Jenny, 1971, et al.
(författare)
-
Galectins as inflammatory mediators.
- 2004
-
Ingår i: Glycoconjugate journal. - 0282-0080. ; 19:7-9, s. 575-81
-
Forskningsöversikt (refereegranskat)abstract
- Over the last decade a vast amount of reports have shown that galectin-1 and galectin-3 are important mediators of inflammation. In this review we describe how the galectins may be involved in several parts of the inflammatory process, including the recruitment of neutrophils into an infected tissue and the recognition and killing of bacteria by activation of the tissue destructive phagocytic respiratory burst. During bacterial infection or aseptic inflammatory processes, galectins are produced and released by e.g. infected epithelium, activated tissue-resident macrophages and endothelial cells. These extracellular galectins may facilitate binding of neutrophils to the endothelium by cross-linking carbohydrates on the respective cells. Further the galectins improve binding of the neutrophil to the extracellular matrix proteins laminin and fibronectin, and are potential chemotactic factors, inducing migration through the extracellular matrix towards the inflammatory focus. When the cells encounter bacteria, galectin-3 could function as an opsonin, cross-linking bacterial lipopolysaccharide or other carbohydrate-containing surface structures to phagocyte surface glycoconjugates. Both galectin-1 and galectin-3 have the capacity to induce a respiratory burst in neutrophils, provided that the cells have been primed by degranulation and receptor upregulation. The reactive oxygen species produced may be destructive to the invading micro-organisms as well as to the surrounding host tissue, pointing out the possible role of galectins, not only in defence toward infection, but also in inflammatory-induced tissue destruction.
|
|
| 4. |
- Almkvist, Jenny, 1971
(författare)
-
Identification of galectins as novel inflammatory mediators
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human neutrophils play important roles in the host defence against invading microorganisms. To eliminate bacteria or other invaders the neutrophils have to leave the bloodstream and cross the endothelium, migrate through the extracellular matrix towards the site of infection and phagocytose the prey to ultimately kill it. By activation of the enzyme complex NADPH-oxidase, the neutrophils produce toxic oxygen metabolites that have bactericidal effects when released into the phagosome, but are tissue destructive if released extracellularly. Galectins are a family of today 14 b-galactoside-binding lectins produced and secreted by a variety of cell types. Some galectins are produced by cells involved in inflammatory processes and the aim of this study was to investigate the interaction of galectin-1 and galectin-3 with human neutrophils with emphasis on activation of the NADPH-oxidase. Both galectin-1 and galectin-3 have the ability to activate the NADPH-oxidase in neutrophils, provided that the cells are primed. Here, priming was achieved either in vivo, by transmigration from the bloodstream and extravasation into the tissue or in vitro by pre-incubating the cells with bacterial lipopolysaccharides or the formylated tripeptide fMLF. Regardless of priming technique, the induced galectin responsiveness was due to mobilisation of receptor-containing intracellular granules to the plasma membrane and subsequent upregulation of galectin receptors on the cell surface. By correlating the mobilisation of granule markers with the ability of galectin-1 to activate the NADPH-oxidase in differently primed cells, the intracellular localisation of the activating receptors in resting cells could be determined to the secretory vesicle and gelatinase granules. This is to be compared to the galectin-3 receptors, which are localised to the gelatinase and specific granules. A novel priming agent employing the same mechanism was also defined. Desialylation of the neutrophil cell surface by Newcastle Disease Virus neuraminidase induced a signal for degranulation resulting in priming for galectins.Based on the above it is evident that the galectins confer pro-inflammatory activities. It is of outmost importance that we increase our understanding of galectin function to define possible points of attack for regulation of the inflammatory process in vivo.
|
|
| 5. |
- Almkvist, Jenny, 1971, et al.
(författare)
-
Newcastle disease virus neuraminidase primes neutrophils for stimulation by galectin-3 and formyl-Met-Leu-Phe
- 2004
-
Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 298:1, s. 74-82
-
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.
|
|
| 6. |
- Carlsson, Susanne, et al.
(författare)
-
Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface.
- 2007
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 17:6, s. 663-76
-
Tidskriftsartikel (refereegranskat)abstract
- Galectin-8 has two different carbohydrate recognition domains (CRDs), the N-terminal Gal-8N and the C-terminal Gal-8C linked by a peptide, and has various effects on cell adhesion and signaling. To understand the mechanism for these effects further, we compared the binding activities of galectin-8 in solution with its binding and activation of cells. We used glycan array analysis to broaden the specificity profile of the two galectin-8 CRDs, as well as intact galectin-8s (short and long linker), confirming the unique preference for sulfated and sialylated glycans of Gal-8N. Using a fluorescence anisotropy assay, we examined the solution affinities for a subset of these glycans, the highest being 50 nM for NeuAcalpha2,3Lac by Gal-8N. Thus, carbohydrate-protein interactions can be of high affinity without requiring multivalency. More importantly, using fluorescence polarization, we also gained information on how the affinity is built by multiple weak interactions between different fragments of the glycan and its carrier molecule and the galectin CRD subsites (A-E). In intact galectin-8 proteins, the two domains act independently of each other in solution, whereas at a surface they act together. Ligands with moderate or weak affinity for the isolated CRDs on the array are bound strongly by intact galectin-8s. Also galectin-8 binding and signaling at cell surfaces can be explained by combined binding of the two CRDs to low or medium affinity ligands, and their highest affinity ligands, such as sialylated galactosides, are not required.
|
|
