uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Nilsson Ekdahl, Kristina
Alternative names
Publications (10 of 122) Show all publications
Mohlin, C., Sandholm, K., Kvanta, A., Nilsson Ekdahl, K. & Johansson, K. (2018). A model to study complement involvement in experimental retinal degeneration. Upsala Journal of Medical Sciences, 123(1), 28-42
Open this publication in new window or tab >>A model to study complement involvement in experimental retinal degeneration
Show others...
2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 28-42Article in journal (Refereed) Published
Abstract [en]

Background: The complement system (CS) plays a role in the pathogenesis of a number of ocular diseases, including diabetic retinopathy (DR), glaucoma, uveitis, and age-related macular degeneration (AMD). Given that many of the complex eye-related degenerative diseases have limited treatment opportunities, we aimed to mimic the in vivo retinal degenerative process by developing a relevant co-culture system.

Method and materials: The adult porcine retina was co-cultured with the spontaneously arising human retinal pigment epithelial cells-19 (ARPE-19).

Results: Inflammatory activity was found after culture and included migrating microglial cells, gliosis, cell death, and CS activation (demonstrated by a minor increase in the secreted anaphylotoxin C3a in co-culture). CS components, including C1q, C3, C4, soluble C5b-9, and the C5a receptor, were expressed in the retina and/or ARPE cells after culture. C1q, C3, and CS regulators such as C4 binding protein (C4BP), factor H (CFH), and factor I (CFI) were secreted after culture.

Discussion: Thus, our research indicates that this co-culturing system may be useful for investigations of the CS and its involvement in experimental neurodegenerative diseases.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
AMD, complement system, ocular diseases, retina, RPE
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-354542 (URN)10.1080/03009734.2018.1431744 (DOI)000428060300004 ()29436895 (PubMedID)
Funder
Swedish Research CouncilStiftelsen Olle Engkvist ByggmästareMedical Research Council of Southeast Sweden (FORSS)
Available from: 2018-06-21 Created: 2018-06-21 Last updated: 2018-06-21Bibliographically approved
Huber-Lang, M., Nilsson Ekdahl, K., Wiegner, R., Fromell, K. & Nilsson, B. (2018). Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions. Seminars in Immunopathology, 40(1), 87-102
Open this publication in new window or tab >>Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions
Show others...
2018 (English)In: Seminars in Immunopathology, ISSN 1863-2297, E-ISSN 1863-2300, Vol. 40, no 1, p. 87-102Article, review/survey (Refereed) Published
Abstract [en]

Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase. This concept review article aims at identifying and describing conditions where the strict system-related control is circumvented. These include clinical settings where massive amounts of proteolytic enzymes are released from tissues, e.g., during pancreatitis or post-traumatic tissue damage, resulting in consumption of the natural substrates of the specific proteases and the available protease inhibitor. Another example of cascade system dysregulation is disseminated intravascular coagulation, with canonical activation of all cascade systems of the blood, also leading to specific substrate and protease inhibitor elimination. The present review explains basic concepts in protease biochemistry of importance to understand clinical conditions with extensive protease activation.

Keywords
Complement system, Proteases, Protease inhibitors, Trauma
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-350204 (URN)10.1007/s00281-017-0646-9 (DOI)000424058800008 ()28900700 (PubMedID)
Funder
German Research Foundation (DFG)Swedish Research Council, 2016-01060; 2016-04519EU, FP7, Seventh Framework Programme, 602699
Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-05-08Bibliographically approved
Nilsson Ekdahl, K., Davoodpour, P., Ekstrand-Hammarström, B., Fromell, K., Hamad, O. A., Hong, J., . . . Nilsson, B. (2018). Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles.. Nanomedicine: Nanotechnology, Biology and Medicine, 14(3), 735-744
Open this publication in new window or tab >>Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles.
Show others...
2018 (English)In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 14, no 3, p. 735-744Article in journal (Refereed) Published
Abstract [en]

Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. alpha-Fe2O3 NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine alpha-Fe2O3 NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The alpha-Fe2O3 NPs exhibited a noticeable toxicity, with kinin/kallikrein activation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
α-Fe2O3, NPsContact/kallikrein system, Innate immunity
National Category
Immunology in the medical area Nano Technology
Identifiers
urn:nbn:se:uu:diva-343471 (URN)10.1016/j.nano.2017.12.008 (DOI)000429528900010 ()
Funder
Swedish Research Council, 2014-3938 2016-2075-5.1 2016-01060 2016-04519EU, FP7, Seventh Framework Programme, 602699AFA Insurance
Note

Joint and equal contribution to senior authorship by Kristina N. Ekdahl, Padideh Davoodpour and Bo Nilsson

Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-06-08Bibliographically approved
Labriere, C., Kondori, N., Caous, J. S., Boomgaren, M., Sandholm, K., Nilsson Ekdahl, K., . . . Svenson, J. (2018). Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines. Paper presented at 7th International Meeting on Antimicrobial Peptides, AUG 25-27, 2017, Univ Copenhagen, Copenhagen, DENMARK. Journal of Peptide Science, 24(7), Article ID e3090.
Open this publication in new window or tab >>Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines
Show others...
2018 (English)In: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 24, no 7, article id e3090Article in journal (Refereed) Published
Abstract [en]

Both pathogenic bacteria and fungi are developing resistance to common antimicrobial treatment at an alarming rate. To counteract this development, it is of essence to develop new classes of antimicrobial agents. One such class is antimicrobial peptides, most of which are derived from the innate immune system. In this study, a series of novel 2,5-diketopiperazines were designed, synthesized, and evaluated for their antimicrobial abilities. The compounds were designed to probe the pharmacophore dictated for short linear mimics of antimicrobial cationic peptides, and as such, the compounds contain a range of cationic and hydrophobic functionalities. Several of the prepared compounds displayed high antimicrobial activities toward bacteria and also against human pathogenic fungi. Of particular interest was the high activity toward fungal strains with an inherent increased resistance toward conventional antifungal agents. The most effective compounds displayed inhibition of Candida glabrata and Candida krusei growth at concentrations between 4 and 8 mu g/mL, which is comparable to commercial antifungal agents in use. Structure activity relationship studies revealed a similar dependence on cationic charge and the volume of the hydrophobic bulk as for linear cationic antimicrobial peptides. Finally, the hemolytic activity of selected compounds was evaluated, which revealed a potential to produce active compounds with attenuation of unwanted hemolysis. The findings highlight the potential of cyclic cationic amphiphilic peptidomimetics as a class of promising compounds for the treatment of infections caused by microorganisms with an increased resistance to conventional antimicrobial agents.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
2, 5-diketopiperazine, antifungal agents, antimicrobial, Candida krusei, MRSA, structure-activity relationship
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-362848 (URN)10.1002/psc.3090 (DOI)000440144700005 ()29845683 (PubMedID)
Conference
7th International Meeting on Antimicrobial Peptides, AUG 25-27, 2017, Univ Copenhagen, Copenhagen, DENMARK
Funder
VINNOVA, 2014-01435The Research Council of Norway, ES508288
Available from: 2018-10-15 Created: 2018-10-15 Last updated: 2018-10-15Bibliographically approved
Fromell, K., Johansson, U., Dührkop, C., Adler, A., Usterud, E., Hamad, O. A., . . . Nilsson, B. (2018). Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3. Paper presented at 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, New Mexico, USA.. Molecular Immunology, 102, 193-193
Open this publication in new window or tab >>Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3
Show others...
2018 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, p. 193-193Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2018
Keywords
Complement C3
National Category
Immunology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-365114 (URN)10.1016/j.molimm.2018.06.167 (DOI)000445313600163 ()
Conference
27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, New Mexico, USA.
Available from: 2018-11-15 Created: 2018-11-15 Last updated: 2018-11-15Bibliographically approved
Nilsson Ekdahl, K., Persson, B., Mohlin, C., Sandholm, K., Skattum, L. & Nilsson, B. (2018). Interpretation of Serological Complement Biomarkers in Disease. Frontiers in Immunology, 9, Article ID 2237.
Open this publication in new window or tab >>Interpretation of Serological Complement Biomarkers in Disease
Show others...
2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 2237Article, review/survey (Refereed) Published
Abstract [en]

Complement systemaberrations have been identified as pathophysiological mechanisms in a number of diseases and pathological conditions either directly or indirectly. Examples of such conditions include infections, inflammation, autoimmune disease, as well as allogeneic and xenogenic transplantation. Both prospective and retrospective studies have demonstrated significant complement-related differences between patient groups and controls. However, due to the low degree of specificity and sensitivity of some of the assays used, it is not always possible to make predictions regarding the complement status of individual patients. Today, there are three main indications for determination of a patient's complement status: (1) complement deficiencies (acquired or inherited); (2) disorders with aberrant complement activation; and (3) C1 inhibitor deficiencies (acquired or inherited). An additional indication is to monitor patients on complement-regulating drugs, an indication which may be expected to increase in the near future since there is now a number of such drugs either under development, already in clinical trials or in clinical use. Available techniques to study complement include quantification of: (1) individual components; (2) activation products, (3) function, and (4) autoantibodies to complement proteins. In this review, we summarize the appropriate indications, techniques, and interpretations of basic serological complement analyses, exemplified by a number of clinical disorders.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
complement, deficiency, activation products, functional test, complement regulatory drugs
National Category
Immunology in the medical area Immunology
Identifiers
urn:nbn:se:uu:diva-369948 (URN)10.3389/fimmu.2018.02237 (DOI)000448107500001 ()30405598 (PubMedID)
Funder
Swedish Research Council, 2016-2075-5.1Swedish Research Council, 2016-04519
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Mohlin, C., Petrus-Reurer, S., Lanner, F., Sandholm, K., Nilsson, P., Nilsson, B. & Nilsson Ekdahl, K. (2018). Is the polarized secretion of complement factor H of importance in age-related macular degeneration?. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI. Investigative Ophthalmology and Visual Science, 59(9)
Open this publication in new window or tab >>Is the polarized secretion of complement factor H of importance in age-related macular degeneration?
Show others...
2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal, Meeting abstract (Other academic) Published
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-366392 (URN)000442932806149 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Funder
Swedish Research Council
Available from: 2018-11-21 Created: 2018-11-21 Last updated: 2018-11-21Bibliographically approved
van Griensven, M., Ricklin, D., Denk, S., Halbgebauer, R., Braun, C. K., Schultze, A., . . . Huber-Lang, M. S. (2018). PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK. Paper presented at 41st Annual Conference on Shock, JUN 09-12, 2018, Scottsdale, AZ. Shock, 49(6, Suppl. 1), 117-118, Article ID P183.
Open this publication in new window or tab >>PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK
Show others...
2018 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 49, no 6, Suppl. 1, p. 117-118, article id P183Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-365172 (URN)10.1097/SHK.0000000000001158 (DOI)000441343800253 ()
Conference
41st Annual Conference on Shock, JUN 09-12, 2018, Scottsdale, AZ
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Knabl, L., Berktold, M., Hamad, O. A., Fromell, K., Chatterjee, S., Speth, C., . . . Orth-Holler, D. (2018). Shiga toxin 2a binds antithrombin and heparin, but does not directly activate platelets. International Journal of Medical Microbiology, 308(7), 969-976
Open this publication in new window or tab >>Shiga toxin 2a binds antithrombin and heparin, but does not directly activate platelets
Show others...
2018 (English)In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 308, no 7, p. 969-976Article in journal (Refereed) Published
Abstract [en]

Escherichia coli-induced hemolytic uremic syndrome (eHUS) is a life-threatening complication of infection with Shiga toxin (Stx), in particular Stx2a-producing Escherichia coli. Enhanced coagulation activation with formation of microthrombi seems to be a key event in development of eHUS. Platelet activation has been postulated as a possible, but controversially debated mechanism. The present study investigated the effect of Stx2a on plasmatic coagulation and platelets. Binding studies were initially performed with ELISA and co-immunoprecipitation and supported by quartz crystal microbalance with dissipation monitoring (QCM-D). Antithrombin (AT) activity was measured using the automated BCS XP (R) system. ROTEM (R) was used for functional coagulation testing. Platelet binding and activation was studied with FACS and light-transmission aggregometry. We found binding of Stx2a to AT, an important inhibitor of blood coagulation, but only a mild albeit significant reduction of AT activity against FXa in the presence of Stx2a. QCM-D analysis also showed binding of Stx2a to heparin and an impaired binding of AT to Stx2a-bound heparin. ROTEM (R) using Stx2a-treated platelet-poor plasma revealed a significant, but only moderate shortening of clotting time. Neither binding nor activation of platelets by Stx2a could be demonstrated. In summary, data of this study suggest that Stx2a binds to AT, but does not induce major effects on plasmatic coagulation. In addition, no interaction with platelets occurred. The well-known non-beneficial administration of heparin in eHUS patients could be explained by the interaction of Stx2a with heparin.

Keywords
Stx2a, Hemolytic uremic syndrome, Plasmatic coagulation, Antithrombin
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-369763 (URN)10.1016/j.ijmm.2018.07.008 (DOI)000448628100027 ()30064820 (PubMedID)
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Fromell, K., Dührkop, C., Kozarcanin, H., Johansson, U., Skjoedt, M.-O., Garred, P., . . . Nilsson, B. (2018). The lectin pathway of complement and the contact/kallikrein system are integrated. Paper presented at 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, New Mexico, USA.. Molecular Immunology, 102, 151-152
Open this publication in new window or tab >>The lectin pathway of complement and the contact/kallikrein system are integrated
Show others...
2018 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, p. 151-152Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2018
Keywords
Lectin pathway, Contact system, Clotting, Fibrin
National Category
Biochemistry and Molecular Biology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-365113 (URN)10.1016/j.molimm.2018.06.071 (DOI)000445313600067 ()
Conference
27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, New Mexico, USA.
Available from: 2018-11-08 Created: 2018-11-08 Last updated: 2018-11-08Bibliographically approved
Organisations

Search in DiVA

Show all publications