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Publications (4 of 4) Show all publications
Duehrkop, C., Leneweit, G., Heyder, C., Fromell, K., Edwards, K., Nilsson Ekdahl, K. & Nilsson, B. (2016). Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions. Colloids and Surfaces B: Biointerfaces, 141, 576-583
Open this publication in new window or tab >>Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions
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2016 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 141, p. 576-583Article in journal (Refereed) Published
Abstract [en]

Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non-coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential. (C) 2016 Elsevier B.V. All rights reserved.

Keywords
Drug delivery system, Cationic liposomes, Surface coating, Novel heparin complex, Complement system
National Category
Biomaterials Science
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-53258 (URN)10.1016/j.colsurfb.2016.02.014 (DOI)000374197700068 ()26897551 (PubMedID)2-s2.0-84958291889 (Scopus ID)
Available from: 2016-06-10 Created: 2016-06-10 Last updated: 2018-11-16Bibliographically approved
Lindblom, R. P. F., Berg, A., Ström, M., Aeinehband, S., Dominguez, C. A., Al Nimer, F., . . . Piehl, F. (2015). Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response. Journal of Neuroinflammation, 12, Article ID 192.
Open this publication in new window or tab >>Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response
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2015 (English)In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 12, article id 192Article in journal (Refereed) Published
Abstract [en]

Background: Activation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking. Methods: Large-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA). Expression of Cr2 in the spinal cord was studied in a separate cohort of DA and PVG rats at different time-points after VRA, and also following sciatic nerve transection (SNT) in the same strains. Consequently, Cr2(-/-) mice and Wt controls were used to further explore the role of Cr2 in the spinal cord following SNT. The in vivo experiments were complemented by astrocyte and microglia cell cultures. Results: Expression of Cr2 in naive spinal cord was low but strongly up regulated at 5-7 days after both VRA and SNT. Levels of Cr2 expression, as well as astrocyte activation, was higher in PVG rats than DA rats following both VRA and SNT. Subsequent in vitro studies proposed astrocytes as the main source of Cr2 expression. A functional role for Cr2 is suggested by the finding that transgenic mice lacking Cr2 displayed increased loss of synaptic nerve terminals following nerve injury. We also detected increased levels of soluble CR2 (sCR2) in the cerebrospinal fluid of rats following VRA. Conclusions: These results demonstrate that local expression of Cr2 in the central nervous system is part of the axotomy reaction and is suggested to modulate subsequent complement mediated effects.

Keywords
Complement system, Complement receptor 2, Neuroinflammation, Neurodegeneration, Synapses
National Category
Immunology in the medical area
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-52094 (URN)10.1186/s12974-015-0413-6 (DOI)000363387700002 ()26502875 (PubMedID)
Available from: 2016-04-15 Created: 2016-04-15 Last updated: 2018-11-16Bibliographically approved
Hamad, O. A., Mitroulis, I., Fromell, K., Kozarcanin, H., Chavakis, T., Ricklin, D., . . . Nilsson, B. (2015). Contact activation of C3 enables tethering between activated platelets and polymorphonuclear leukocytes via CD11b/CD18. Thrombosis and Haemostasis, 114(6), 1207-1217
Open this publication in new window or tab >>Contact activation of C3 enables tethering between activated platelets and polymorphonuclear leukocytes via CD11b/CD18
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2015 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 114, no 6, p. 1207-1217Article in journal (Refereed) Published
Abstract [en]

Complement component C3 has a potential role in thrombotic pathologies. It is transformed, without proteolytic cleavage, into C3(H2O) upon binding to the surface of activated platelets. We hypothesise that C3(H2O) bound to activated platelets and to platelet-derived microparticles (PMPs) contributes to platelet-PMN complex (PPC) formation and to the binding of PMPs to PMNs. PAR-1 activation of platelets in human whole blood from normal individuals induced the formation of CD16(+)/CD42a(+) PPC. The complement inhibitor compstatin and a C5a receptor antagonist inhibited PPC formation by 50 %, while monoclonal antibodies to C3(H2O) or anti-CD11b inhibited PPC formation by 75-100 %. Using plasma protein-depleted blood and blood from a C3-deficient patient, we corroborated the dependence on C3, obtaining similar results after reconstitution with purified C3. By analogy with platelets, PMPs isolated from human serum were found to expose C3(H2O) and bind to PMNs. This interaction was also blocked by the anti-C3(H2O) and anti-CD11b monoclonal antibodies, indicating that C3(H2O) and CD11b are involved in tethering PMPs to PMNs. We confirmed the direct interaction between C3(H2O) and CD11b by quartz crystal microbalance analysis using purified native C3 and recombinant CD11b/CD18 and by flow cytometry using PMP and recombinant CD11b. Transfectants expressing CD11b/CD18 were also shown to specifically adhere to surface-bound C3(H2O). We have identified contact-activated C3(H2O) as a novel ligand for CD11b/CD18 that mediates PPC formation and the binding of PMPs to PMNs. Given the various roles of C3 in thrombotic reactions, this finding is likely to have important pathophysiological implications.

Keywords
Complement C3, platelets, microparticles, PMN, platelet-leukocyte complex
National Category
Biochemistry and Molecular Biology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-48814 (URN)10.1160/TH15-02-0162 (DOI)000365769200014 ()26293614 (PubMedID)2-s2.0-84983108465 (Scopus ID)
Available from: 2016-01-19 Created: 2016-01-15 Last updated: 2018-11-16Bibliographically approved
Klapper, Y., Maffre, P., Shang, L., Nilsson Ekdahl, K., Nilsson, B., Hettler, S., . . . Nienhaus, G. U. (2015). Low affinity binding of plasma proteins to lipid-coated quantum dots as observed by in situ fluorescence correlation spectroscopy. Nanoscale, 7(22), 9980-9984
Open this publication in new window or tab >>Low affinity binding of plasma proteins to lipid-coated quantum dots as observed by in situ fluorescence correlation spectroscopy
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2015 (English)In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 7, no 22, p. 9980-9984Article in journal (Refereed) Published
Abstract [en]

Protein binding to lipid-coated nanoparticles has been pursued quantitatively by using fluorescence correlation spectroscopy. The binding of three important plasma proteins to lipid-enwrapped quantum dots (QDs) shows very low affinity, with an apparent dissociation coefficient in the range of several hundred micromolar. Thus, the tendency to adsorb is orders of magnitude weaker than for QDs coated with dihydrolipoic acid.

National Category
Biomaterials Science
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-52095 (URN)10.1039/c5nr01694k (DOI)000355560200004 ()25975280 (PubMedID)2-s2.0-84930323677 (Scopus ID)
Available from: 2016-04-15 Created: 2016-04-15 Last updated: 2018-11-16Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-0057-2730

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