| 1. |
- Danielsson, Ravi, et al.
(författare)
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Aluminium Adjuvants : a Nanomaterial used as Adjuvants in Human Vaccines for Decades
- 2018
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Ingår i: Open Biotechnology Journal. - : Bentham eBooks. - 1874-0707. ; 12, s. 140-153
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Forskningsöversikt (refereegranskat)abstract
- Background: Aluminium salts have been used for decades in vaccines as adjuvants to facilitate the adaptive immune response against co-administered antigens. Two types of aluminium adjuvant are mostly used, aluminium oxyhydroxide and aluminium hydroxyphosphate. Both types of aluminium adjuvant consist of nanoparticles that form loose, micrometre sized aggregates at circumneutral pH. Aluminium adjuvants constitute a well-documented example of administration of nanomaterials to humanswith infrequent side effects and a safety record generally regarded as excellent. However, despite its prolonged use in human and veterinary medicine, the mechanisms behind the enhanced response and the immune stimulatory effect are still by and large unknown. Methods: The present paper reviews existing ideas regarding the immunostimulatory effects of aluminium adjuvants, with a focus on the induction of an inflammatory response by cellular stress. Reviewed information was obtained from peer-reviewed scientific papers published in 1988 to date with one exception, a paper published 1931. Results: Cellular stress causes extra cellular signalling of danger associated molecular patterns (DAMPs) and upon phagocytosis of aluminium adjuvants the cells need to manage the ingested particles. Conclusion: A persistent intracellular accumulation of aluminium adjuvants will be a solid depository of sparingly soluble aluminium salts maintaining a constant concentration of Al3+ ions in the cytoplasm and this will affect multiple biochemical processes. The cell will be under constant stress and DAMP signalling will occur and we would like to suggest the maintenance of a constant concentration Al3+ ions in the cytoplasm as a general underlying feature of the immune stimulation properties of aluminium adjuvants.
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| 2. |
- Danielsson, Ravi, et al.
(författare)
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Aluminium adjuvants in vaccines : A way to modulate the immune response
- 2021
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Ingår i: Seminars in Cell and Developmental Biology. - : Elsevier. - 1084-9521 .- 1096-3634. ; 115, s. 3-9
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Tidskriftsartikel (refereegranskat)abstract
- Aluminium salts have been used as adjuvants in vaccines for almost a century, but still no clear understanding of the mechanisms behind the immune stimulating properties of aluminium based adjuvants is recognized. Aluminium adjuvants consist of aggregates and upon administration of a vaccine, the aggregates will be recognized and phagocytosed by sentinel cells such as macrophages or dendritic cells. The adjuvant aggregates will persist intracellularly, maintaining a saturated intracellular concentration of aluminium ions over an extended time. Macrophages and dendritic cells are pivotal cells of the innate immune system, linking the innate and adaptive immune systems, and become inflammatory and antigen-presenting upon activation, thus mediating the initiation of the adaptive immune system. Both types of cell are highly adaptable, and this review will discuss and highlight how the occurrence of intracellular aluminium ions over an extended time may induce the polarization of macrophages into inflammatory and antigen presenting M1 macrophages by affecting the: endosomal pH; formation of reactive oxygen species (ROS); stability of the phagosomal membrane; release of damage associated molecular patterns (DAMPs); and metabolism (metabolic re-programming). This review emphasizes that a persistent intracellular presence of aluminium ions over an extended time has the potential to affect the functionality of sentinel cells of the innate immune system, inducing polarization and activation. The immune stimulating properties of aluminium adjuvants is presumably mediated by several discrete events, however, a persistent intracellular presence of aluminium ions appears to be a key factor regarding the immune stimulating properties of aluminium based adjuvants.
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| 3. |
- Danielsson, Ravi, et al.
(författare)
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Aqueous polymer two-phase systems and their use in fragmentation and separation of biological membranes for the purpose of mapping the membrane structure.
- 2013
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Ingår i: Preparative Biochemistry & Biotechnology. - : Informa UK Limited. - 1532-2297 .- 1082-6068. ; 43:5, s. 512-525
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Tidskriftsartikel (refereegranskat)abstract
- When solutions of two different polymers are mixed, phase separation often occurs even at low concentrations of polymers. One polymer usually collects in one phase and the other polymer in the other phase. When water is used as solvent, two aqueous, immiscible, phases are obtained. The same holds for aqueous mixtures of a salt and a polymer. Such aqueous two-phase systems (ATPS) are very useful for separation of high-molecular-weight biomolecules such as proteins and nucleic acids and also for cells, cell organelles, and membrane vesicles. The phase systems can be made highly selective and they are also mild toward biomolecules and cell particles. In this review we describe how ATPS can be used for fragmentation and separation analyses of biological membranes and how this can be used for mapping of the photosynthetic membrane, the thylakoid, of green leaves.
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| 4. |
- Danielsson, Ravi, et al.
(författare)
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Dimeric and monomeric organization of photosystem II - Distribution of five distinct complexes in the different domains of the thylakoid membrane
- 2006
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 281:20, s. 14241-14249
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Tidskriftsartikel (refereegranskat)abstract
- The supramolecular organization of photosystem II (PSII) was characterized in distinct domains of the thylakoid membrane, the grana core, the grana margins, the stroma lamellae, and the so-called Y100 fraction. PSII supercomplexes, PSII core dimers, PSII core monomers, PSII core monomers lacking the CP43 subunit, and PSII reaction centers were resolved and quantified by blue native PAGE, SDS-PAGE for the second dimension, and immunoanalysis of the D1 protein. Dimeric PSII (PSII supercomplexes and PSII core dimers) dominate in the core part of the thylakoid granum, whereas the monomeric PSII prevails in the stroma lamellae. Considerable amounts of PSII monomers lacking the CP43 protein and PSII reaction centers (D1-D2-cytochrome b(559) complex) were found in the stroma lamellae. Our quantitative picture of the supramolecular composition of PSII, which is totally different between different domains of the thylakoid membrane, is discussed with respect to the function of PSII in each fraction. Steady state electron transfer, flash-induced fluorescence decay, and EPR analysis revealed that nearly all of the dimeric forms represent oxygen-evolving PSII centers. PSII core monomers were heterogeneous, and a large fraction did not evolve oxygen. PSII monomers without the CP43 protein and PSII reaction centers showed no oxygen-evolving activity.
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| 5. |
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| 6. |
- Danielsson, Ravi, et al.
(författare)
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Fragmentation and separation analysis of the photosynthetic membrane from spinach.
- 2009
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Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728. ; 1787:1, s. 25-36
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Tidskriftsartikel (refereegranskat)abstract
- Membrane vesicles, originating from grana, grana core (appressed grana regions), grana margins and stroma lamellae/end membranes, were analysed by counter current distribution (CCD) using aqueous dextran-polyethylene glycol two-phase systems. Each vesicle population gave rise to distinct peaks in the CCD diagram representing different vesicle subpopulations. The grana vesicles and grana core vesicles each separated into 3 different subpopulations having different chlorophyll a/b ratios and PSI/PSII ratios. Two of the grana core subpopulations had a chlorophyll a/b ratio of 2.0 and PSI/PSII ratio of 0.10 and are among the most PSII enriched thylakoid vesicle preparation obtained so far by a non detergent method. The margin vesicles separated into 3 different populations, with about the same chlorophyll a/b ratios, but different fluorescence emission spectra. The stroma lamellae/end membrane vesicles separated into 4 subpopulations. Plastoglobules, connected to membrane vesicles, were highly enriched in 2 of these subpopulations and it is proposed that these 2 subpopulations originate from stroma lamellae while the 2 others originate from end membranes. Fragmentation and separation analysis shows that the margins of grana constitute a distinct domain of the thylakoid and also allows the estimation of the chlorophyll antenna sizes of PSI and PSII in different thylakoid domains.
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| 7. |
- Danielsson, Ravi, et al.
(författare)
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Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:5
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Tidskriftsartikel (refereegranskat)abstract
- Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants is not fully understood. Needless to say, extending the knowledge of the immune-stimulating properties of aluminum-based adjuvants is of utmost importance in the development of new, safer, and efficient vaccines. To further our knowledge of the mode of action of aluminum-based adjuvants, the prospect of metabolic reprogramming of macrophages upon phagocytosis of aluminum-based adjuvants was investigated. Macrophages were differentiated and polarized in vitro from human peripheral monocytes and incubated with the aluminum-based adjuvant Alhydrogel((R)). Polarization was verified by the expression of CD markers and cytokine production. In order to recognize adjuvant-derived reprogramming, macrophages were incubated with Alhydrogel((R)) or particles of polystyrene as control, and the cellular lactate content was analyzed using a bioluminescent assay. Quiescent M0 macrophages, as well as alternatively activated M2 macrophages, exhibited increased glycolytic metabolism upon exposure to aluminum-based adjuvants, indicating a metabolic reprogramming of the cells. Phagocytosis of aluminous adjuvants could result in an intracellular depot of aluminum ions, which may induce or support a metabolic reprogramming of the macrophages. The resulting increase in inflammatory macrophages could thus prove to be an important factor in the immune-stimulating properties of aluminum-based adjuvants.
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| 8. |
- Danielsson, Ravi
(författare)
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On the lateral organisation of the thylakoid membrane
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this work the lateral heterogeneity of the thylakoid membrane was investigated by quantifying the amount of photosystem I (PSI), photosystem II (PSII) and some PSII complexes and PSII proteins in different domains of the thylakoid. Grana, grana core, grana margins and stroma lamellae + end fractions were obtained by sonication and separation in a non-detergent, aqueous polymer two-phase system. Y-100 was obtained by Yeda press and centrifugation. EPR spectroscopy was used to quantify PSI (P700+) and PSII (YD·) in the different fractions. These measurements showed a successively increasing amount of PSI from grana core, grana, grana margins and stroma lamellae + end membranes to Y-100. On the contrary the amount of PSII is decreased successively from grana core to Y-100. The ratio PSI/PSII increases from 0,25 in grana core to 13 in Y-100. For the entire thylakoid the PSI/PSII ratio is 1,13. Gel electrophoresis was performed to trace five PSII complexes (supercomplexes, dimers, monomers with CP43 and monomers without CP43, and core reaction centres) in the different fractions of the thylakoid. These were then quantified by western blotting. The supercomplexes are most common in grana core and the fragments of the complexes are most common in Y-100, in a gradient through the fractions. This gives strong support to the notion of a lateral transport of PSII centres from grana core to Y-100 and back again, in a repair process. Thirteen PSII proteins were also analysed and quantified in the different fractions. PsbS, PsbW, PsbZ were overrepresented in grana or grana core and absent or nearly absent in Y-100. It agrees with their assumed function of preserving and stabilising the fully developed PSII complexes in grana core. Using counter-current distribution, a diagram was obtained showing heterogeneity within all the sub-fractions according to their surface properties.
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| 9. |
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| 10. |
- Danielsson, Ravi, et al.
(författare)
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Quantification, of photosystem I and II in different parts of the thylakoid membrane from spinach
- 2004
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Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728. ; 1608:1, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Electron paramagnetic resonance (EPR) was used to quantify Photosystem I (PSI) and PSII in vesicles originating from a series of well-defined but different domains of the thylakoid membrane in spinach prepared by non-detergent techniques. Thylakoids from spinach were fragmented by sonication and separated by aqueous polymer two-phase partitioning into vesicles originating from grana and stroma lamellae. The grana vesicles were further sonicated and separated into two vesicle preparations originating from the grana margins and the appressed domains of grana (the grana core), respectively. PSI and PSII were determined in the same samples from the maximal size of the EPR signal from P700(+) and Y-D(.), respectively. The following PSI/PSII ratios were found: thylakoids, 1.13; grana vesicles, 0.43; grana core, 0.25; grana margins, 1.28; stroma lamellae 3.10. In a sub-fraction of the stroma lamellae, denoted Y-100, PSI was highly enriched and the PSI/PSII ratio was 13. The antenna size of the respective photosystems was calculated from the experimental data and the assumption that a PSII center in the stroma lamellae (PSIIbeta) has an antenna size of 100 Ch1. This gave the following results: PSI in grana margins (PSIalpha) 300, PSI (PSIbeta) in stroma lamellae 214, PSII in grana core (PSIIalpha) 280. The results suggest that PSI in grana margins have two additional light-harvesting complex 11 (LHCII) trimers per reaction center compared to PSI in stroma lamellae, and that PSII in grana has four LHCII trimers per monomer compared to PSII in stroma lamellae. Calculation of the total chlorophyll associated with PSI and PSII, respectively, suggests that more chlorophyll (about 10%) is associated with PSI than with PSII. (C) 2003 Elsevier B.V. All rights reserved.
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