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- Bengtson, Per
(författare)
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Carbohydrate dependent adhesion of leukocytes and the role of fucosyltransferase VII
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Galectins, E-and P-selectins are carbohydrate-binding proteins that are up regulated at inflammatory lesions. Selectins expressed ou the activated endothelium mediate transient binding to leukocyte ligands that require sequential action of α 2,3-sialyltransferases and a 1,3-fucosyltransferases. ln leukocytes α1,3 fucosyltransferase VII adds fucose to α 2,3- sialylated lactosarnine acceptors in the final step of the biosynthesis of the selectin binding epitope sialyl Lewis x.The finding of low sialyl Lewis x expression in polymorphonuclear leukocytes from a patient with ulcerative colitis led to the discovery of a missense mutation (G329A) in the human gene coding for α1,3 fucosyltransferase VII, FUT7. Studies including enzymatic and immunochemical analysis oftransfected cell lines and isolated polymorphonuclear leukocytes from patients confirmed that this mutation impair the ability of α1,3 fucosyltransferase VII to synthesize sialyl Lewis x. The frequency of the mutation were measured in a mixed Swedish population and found to be -1 %. One individual carrying the FUT7-G329A mutation homozygously was identified. This individual suffered from ulcer disease, noninsulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjögren's syndrome, but the relationship between disease and the mutation is not established.Studies using an in vitro flow chamber assay showed that transfected B-lymphoma cells and Epstein-Barr virus transformed B cells only transcribing FUT7-G329A were not able to interact with E-selectin during flow whereas polymorphonuclear leukocytes from the FUT7-G329A homozygous individual interacted well with both P- and E selectin during flow. The mRNA level of the fucosyltransferase IV coding gene, FUT4, was found to be elevated in the homozygous individual, which resulted in elevated levels ofthe CD65s epitope. However, transfected B-lymphoma cells and Epstein- Barr virus transformed cells did not show a similar elevation of FUT4 mRNA. In in vitro studies galectin-1 and- 3 were observed to be able to recruit polymorphonuclear leukocytes during flow. This thesis gives further insight into the molecular mechanisms leading to carbohydrate dependent dynamic adhesion between polymorphonuclear leukocytes and lectins during inflammation.
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| 2. |
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| 3. |
- Bengtson, Per, et al.
(författare)
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Identification of a Missense Mutation (G329A; Arg110→ Gln) in the Human FUT7 Gene
- 2001
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 276:34, s. 31575-31582
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Tidskriftsartikel (refereegranskat)abstract
- The human FUT7 gene codes for the α1,3-fucosyltransferase VII (Fuc-TVII), which is involved in the biosynthesis of the sialyl Lewis x (SLex) epitope on human leukocytes. The FUT7 gene has so far been considered to be monomorphic. Neutrophils isolated from patients with ulcerative colitis were examined for apparent alterations in protein glycosylation patterns by Western blot analysis using monoclonal antibodies directed against SLex and SLex-related epitopes. One individual showed lower levels of SLex expression and an elevated expression of CD65s compared to controls. The coding regions of the FUT7 gene from this individual were cloned, and a G329A point mutation (Arg110 → Gln) was found in one allele, whereas the other FUT7 allele was wild type. No Fuc-TVII enzyme activity was detected in COS-7 cells transiently transfected with the mutated FUT7 construct. TheFUT7 Arg110 is conserved in all previously cloned vertebrate α1,3-fucosyltransferases. Polymerase chain reaction followed by restriction enzyme cleavage was used to screen 364 unselected Caucasians for the G329A mutation, and a frequency of ≤1% for this mutation was found (3 heterozygotes). Genetic characterization of the family members of one of the additional heterozygotes identified one individual carrying the G329A mutation in both FUT7alleles. Peripheral blood neutrophils of this homozygously mutated individual showed a lowered expression of SLex and an elevated expression of CD65s when analyzed by Western blot and flow cytometry. The homozygous individual was diagnosed with ulcer disease, non-insulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjögren's syndrome but had no history of recurrent bacterial infections or leukocytosis.
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| 4. |
- Bengtson, Per
(författare)
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Microbial mobilization and immobilization of soil nitrogen
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microorganisms in forest ecosystems normally recycle nitrogen (N), such that gaseous losses and leaching are limited. Mobilization of organic N, including microbial N, and immobilization of inorganic N, especially NH4+, are the quantitatively most important N transformation processes. Various factors influence their rates, e.g. the amount of carbon and nitrogen, temperature, moisture, and the microbial biomass and activity. The factors are adressed in the thesis with the ambition to suggest mechanistic explanations for their influence on nitrogen mobilization and immobilization rates. The mineralization and immobilization rates are not dependent on the concentration of carbon or nitrogen per se, but rather on the microbial biomass and its activity. This may invalidate the use of first order kinetics to describe mobilization and immobilization rates. Earlier claims that mineralization and immobilization rates are dependent on the concentration of carbon and nitrogen may have overseen the dependence of the microbial biomass on the soil organic matter content. Moisture, temperature, and the quality of the utilized organic matter appear to determine the activity of the microorganisms. Mobilization of microbially bound N seem to occur mainly as a result of predation and drying-rewetting cycles, since microorganisms have an efficient intracellular recycling of nitrogen, especially at low ammonium concentrations. Thus, mobilization and remineralization of microbial nitrogen by other processes than predation and drying-rewetting cycles is likely to occur only when conditions promote high growth rates, i.e. when microorganisms are not substrate limited and temperature and moisture conditions are favourable. The main factors determining microbial mobilization and immobilization of soil N are therefore the size of the microbial biomass, its activity, and the quality of the growth substrate. Those three factors in turn seem to be dependent on soil SOM content, predation, drying-rewetting cycles, temperature, and soil water content.
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| 5. |
- Bengtson, Per, et al.
(författare)
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Polymorphonuclear Leukocytes from Individuals Carrying the G329A Mutation in the α1,3-Fucosyltransferase VII Gene (FUT7) Roll on E- and P-Selectins
- 2002
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 169:7, s. 3940-3946
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Tidskriftsartikel (refereegranskat)abstract
- We recently identified several individuals carrying a missense mutation (G329A; Arg110-Gln) in the FUT7 gene encoding fucosyltransferase VII. This enzyme is involved in the biosynthesis of the sialyl Lewis x (Lex) epitope on human leukocytes, which has been identified as an important component of leukocyte ligands for E- and P-selectin. No enzyme activity was measurable in expression studies in COS-7 cells using the mutated FUT7 construct. One of the identified individuals carried this mutation homozygously. Flow cytometry analysis of polymorphonuclear leukocytes (PMN) from this individual showed a nearly complete absence of staining with mAbs directed against sialyl Lex and a diminished staining with an E-selectin IgG chimera. However, staining with P-selectin IgG chimera and Abs directed against P-selectin glycoprotein ligand-1 was not affected by the mutation. PMN from the homozygously mutated individual was further analyzed in an in vitro flow chamber assay. The number of rolling PMN and the rolling velocities on both E- and P-selectin were in the range of PMN from nonmutated individuals. FUT4 and FUT7 mRNA was quantified in PMN isolated from individuals carrying the FUT7 mutation. It was found that PMN from both FUT7 homozygously and heterozygously mutated individuals exhibited an elevated expression of FUT4 mRNA compared with PMN from FUT7 nonmutated individuals. The elevated expression of fucosyltransferase IV was reflected as an increased expression of the Lex and CD65s Ags on PMN from these individuals. The significance of the mutation was supported by transfection of BJAB cells.
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| 6. |
- Bengtsson, Göran, et al.
(författare)
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Gross nitrogen mineralization-, immobilization-, and nitrification rates as a function of soil C/N ratio and microbial activity
- 2003
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Ingår i: Soil Biology & Biochemistry. - 0038-0717. ; 35:1, s. 143-154
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Tidskriftsartikel (refereegranskat)abstract
- A laboratory experiment was designed to challenge the idea that the ON ratio of forest soils may control gross N immobilization, mineralization, and nitrification rates. Soils were collected from three deciduous forests sites varying in C/N ratio between 15 and 27. They were air-dried and rewetted to induce a burst of microbial activity. The N transformation rates were calculated from an isotope dilution and enrichment procedure, in which (NH4Cl)-N-15 or (NaNO3)-N-15 was repeatedly added to the soils during 7 days of incubation. The experiments suggested that differences in gross nitrogen immobilization and mineralization rates between the soils were more related to the respiration rate and ATP content than to the C/N ratio. Peaks of respiration and ATP content were followed by high rates of mineralization and immobilization, with 1-2 days of delay. The gross immobilization of NH4+ was dependent on the gross mineralization and one to two orders of magnitude larger than the gross NO3- immobilization. The gross nitrification rates were negatively related to the ATP content and the C/N ratio and greatly exceeding the net nitrification rates. Taken together, the observations suggest that leaching of nitrate from forest soils may be largely dependent on the density and activity of the microbial community.
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