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Mohlin, Camilla
Publications (10 of 29) Show all publications
Nilsson Ekdahl, K., Fromell, K., Mohlin, C., Teramura, Y. & Nilsson, B. (2019). A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity. Science and Technology of Advanced Materials, 20(1), 688-698
Open this publication in new window or tab >>A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity
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2019 (English)In: Science and Technology of Advanced Materials, ISSN 1468-6996, E-ISSN 1878-5514, Vol. 20, no 1, p. 688-698Article, review/survey (Refereed) Published
Abstract [en]

In this review article, we focus on activation of the soluble components of the innate immune system triggered by nonbiological compounds and stress variances in activation due to the difference in size between nanoparticles (NPs) and larger particles or bulk material of the same chemical and physical composition. We then discuss the impact of the so-called protein corona which is formed on the surface of NPs when they come in contact with blood or other body fluids. For example, NPs which bind inert proteins, proteins which are prone to activate the contact system (e.g., factor XII), which may lead to clotting and fibrin formation or the complement system (e.g., IgG or C3), which may result in inflammation and vascular damage. Furthermore, we describe a whole blood model which we have developed to monitor activation and interaction between different components of innate immunity: blood protein cascade systems, platelets, leukocytes, cytokine generation, which are induced by NPs. Finally, we describe our own studies on innate immunity system activation induced by three fundamentally different species of NPs (two types of engineered NPs and diesel NPs) as demonstrator of the utility of an initial determination of the composition of the protein corona formed on NPs exposed to ethylenediaminetetraacetic acid (EDTA) plasma and subsequent analysis in our whole blood model. [GRAPHICS] .

Place, publisher, year, edition, pages
Taylor & Francis Group, 2019
Keywords
Coagulation system, complement system, contact, kallikrein system, inflammation, innate immunity, nanoparticles, protein corona, screening, toxicity, whole blood model
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-86907 (URN)10.1080/14686996.2019.1625721 (DOI)000472611100001 ()31275460 (PubMedID)2-s2.0-85067849252 (Scopus ID)
Available from: 2019-07-18 Created: 2019-07-18 Last updated: 2019-08-29Bibliographically approved
Nilsson Ekdahl, K., Mohlin, C., Adler, A., Aman, A., Manivel, V. A., Sandholm, K., . . . Nilsson, B. (2019). Is generation of C-3(H2O) necessary for activation of the alternative pathway in real life?. Paper presented at 17th European Meeting on Complement in Human Disease (EMCHD), 2019, Madrid, SPAIN. Molecular Immunology, 114, 353-361
Open this publication in new window or tab >>Is generation of C-3(H2O) necessary for activation of the alternative pathway in real life?
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2019 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 114, p. 353-361Article in journal (Refereed) Published
Abstract [en]

In the alternative pathway (AP) an amplification loop is formed, which is strictly controlled by various fluid-phase and cell-bound regulators resulting in a state of homeostasis. Generation of the "C3b-like" C3(H2O) has been described as essential for AP activation, since it conveniently explains how the initial fluid-phase AP convertase of the amplification loop is generated. Also, the AP has a status of being an unspecific pathway despite thorough regulation at different surfaces. During complement attack in pathological conditions and inflammation, large amounts of C3b are formed by the classical/lectin pathway (CP/LP) convertases. After the discovery of LP's recognition molecules and its tight interaction with the AP, it is increasingly likely that the AP acts in vivo mainly as a powerful amplification mechanism of complement activation that is triggered by previously generated C3b molecules initiated by the binding of specific recognition molecules. Also in many pathological conditions caused by a dysregulated AP amplification loop such as paroxysmal nocturnal hemoglobulinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), C3b is available due to minute LP and CP activation and/or generated by non-complement proteases. Therefore, C3(H2O) generation in vivo may be less important for AP activation during specific attack or dysregulated homeostasis, but may be an important ligand for C3 receptors in cell-cell interactions and a source of C3 for the intracellular complement reservoir.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Complement system, C-3(H2O), Conformation, Analysis, Proteases, Alternative pathway
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-89867 (URN)10.1016/j.molimm.2019.07.032 (DOI)000490625600041 ()31446306 (PubMedID)
Conference
17th European Meeting on Complement in Human Disease (EMCHD), 2019, Madrid, SPAIN
Available from: 2019-10-31 Created: 2019-10-31 Last updated: 2019-10-31Bibliographically approved
Eriksson, O., Mohlin, C., Nilsson, B. & Nilsson Ekdahl, K. (2019). The Human Platelet as an Innate Immune Cell: Interactions Between Activated Platelets and the Complement System. Frontiers in Immunology, 10, 1-16, Article ID 1590.
Open this publication in new window or tab >>The Human Platelet as an Innate Immune Cell: Interactions Between Activated Platelets and the Complement System
2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, p. 1-16, article id 1590Article, review/survey (Refereed) Published
Abstract [en]

Platelets play an essential role in maintaining homeostasis in the circulatory system after an injury by forming a platelet thrombus, but they also occupy a central node in the intravascular innate immune system. This concept is supported by their extensive interactions with immune cells and the cascade systems of the blood. In this review we discuss the close relationship between platelets and the complement system and the role of these interactions during thromboinflammation. Platelets are protected from complement-mediated damage by soluble and membrane-expressed complement regulators, but they bind several complement components on their surfaces and trigger complement activation in the fluid phase. Furthermore, localized complement activation may enhance the procoagulant responses of platelets through the generation of procoagulant microparticles by insertion of sublytic amounts of C5b9 into the platelet membrane. We also highlight the role of post-translational protein modifications in regulating the complement system and the critical role of platelets in driving these reactions. In particular, modification of disulfide bonds by thiol isomerases and protein phosphorylation by extracellular kinases have emerged as important mechanisms to fine-tune complement activity in the platelet microenvironment. Lastly, we describe disorders with perturbed complement activation where part of the clinical presentation includes uncontrolled platelet activation that results in thrombocytopenia, and illustrate how complement-targeting drugs are alleviating the prothrombotic phenotype in these patients. Based on these clinical observations, we discuss the role of limited complement activation in enhancing platelet activation and consider how these drugs may provide opportunities for further dissecting the complex interactions between complement and platelets.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
complement, platelets, lectin pathway, disulfides, phosphorylation, thiol isomerases, innate immunity
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-86981 (URN)10.3389/fimmu.2019.01590 (DOI)000474774200001 ()2-s2.0-85069449525 (Scopus ID)
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-08-29Bibliographically approved
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.
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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, 2018
Keywords
AMD, RPE, complement system, ocular diseases, retina
National Category
Immunology in the medical area
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-71489 (URN)10.1080/03009734.2018.1431744 (DOI)000428060300004 ()29436895 (PubMedID)2-s2.0-85041902488 (Scopus ID)
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2019-08-29Bibliographically 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
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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. α-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 α-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 α-Fe2O3 NPs exhibited a noticeable toxicity, with kinin/kallikreinactivation, 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
Contact/kallikrein system, Innate immunity, α-Fe(2)O(3) NPs
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-73041 (URN)10.1016/j.nano.2017.12.008 (DOI)000429528900010 ()29277639 (PubMedID)2-s2.0-85041807110 (Scopus ID)
Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2019-08-29Bibliographically approved
Mohlin, C., Delbro, D., Kvanta, A. & Johansson, K. (2018). Evaluation of Congo Red Staining in Degenerating Porcine Photoreceptors In Vitro: Protective Effects by Structural and Trophic Support. Journal of Histochemistry and Cytochemistry, 66(9)
Open this publication in new window or tab >>Evaluation of Congo Red Staining in Degenerating Porcine Photoreceptors In Vitro: Protective Effects by Structural and Trophic Support
2018 (English)In: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 66, no 9Article in journal (Refereed) Published
Abstract [en]

Congo red (CR) is a histological stain used for the detection of extracellular amyloids mediating various neurodegenerative diseases. Given that damaged photoreceptors appear to degenerate similarly to other nerve cells, CR staining was evaluated in experimentally injured porcine retina. CR staining appeared mostly as discrete cytosolic deposits with no obvious plaque formation during the investigated time period. Increases of CR labeling coincided temporally with the known accumulation of mislocalized opsins and increases of cell death. Coculture, either with human retinal pigment epithelium (ARPE) or human neural progenitor (ReN) cells, was accompanied by a significant reduction of CR labeling. Of particular interest was the reduction of CR labeling in cone photoreceptors, which are important for the perception of color and fine details and afflicted in age-related macular degeneration (AMD). Electron microscopy revealed inclusions in the inner segment, cell body, and occasionally synaptic terminals of photoreceptor cells in cultured specimens. Closer examinations indicated the presence of different types of inclusions resembling protein aggregates as well as inclusion bodies. The current results indicate that injury-related response resulted in accumulation of CR deposits in photoreceptor cells, and that trophic and/or structural support attenuated this response.

Place, publisher, year, edition, pages
Sage Publications, 2018
Keywords
Congo red, electron microscopy, fluorescence microscopy, photoreceptor, retina
National Category
Biochemistry and Molecular Biology Structural Biology
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-77723 (URN)10.1369/0022155418768222 (DOI)000443345700002 ()29624116 (PubMedID)2-s2.0-85045027011 (Scopus ID)
Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2019-08-29Bibliographically 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
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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
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-78739 (URN)10.3389/fimmu.2018.02237 (DOI)000448107500001 ()2-s2.0-85055834488 (Scopus ID)
Available from: 2018-11-08 Created: 2018-11-08 Last updated: 2019-08-29Bibliographically approved
Mohlin, C., Petrus-Reurer, S., Lanner, F., Sandholm, K., Nilsson, P. H., 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?
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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
Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018
National Category
Ophthalmology
Research subject
Natural Science, Optometry
Identifiers
urn:nbn:se:lnu:diva-78425 (URN)000442932806149 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2018-11-16Bibliographically approved
Biglarnia, A.-R., Huber-Lang, M., Mohlin, C., Nilsson Ekdahl, K. & Nilsson, B. (2018). The multifaceted role of complement in kidney transplantation. Nature Reviews Nephrology, 14(12), 767-781
Open this publication in new window or tab >>The multifaceted role of complement in kidney transplantation
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2018 (English)In: Nature Reviews Nephrology, ISSN 1759-5061, E-ISSN 1759-507X, Vol. 14, no 12, p. 767-781Article, review/survey (Refereed) Published
Abstract [en]

Increasing evidence indicates an integral role for the complement system in the deleterious inflammatory reactions that occur during critical phases of the transplantation process, such as brain or cardiac death of the donor, surgical trauma, organ preservation and ischaemia-reperfusion injury, as well as in humoral and cellular immune responses to the allograft. Ischaemia is the most common cause of complement activation in kidney transplantation and in combination with reperfusion is a major cause of inflammation and graft damage. Complement also has a prominent role in antibody-mediated rejection (ABMR) owing to ABO and HL A incompatibility, which leads to devastating damage to the transplanted kidney. Emerging drugs and treatment modalities that inhibit complement activation at various stages in the complement cascade are being developed to ameliorate the damage caused by complement activation in transplantation. These promising new therapies have various potential applications at different stages in the process of transplantation, including inhibiting the destructive effects of ischaemia and/or reperfusion injury, treating ABMR, inducing accommodation and modulating the adaptive immune response.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-78998 (URN)10.1038/s41581-018-0071-x (DOI)000450235200011 ()30367174 (PubMedID)2-s2.0-85055731914 (Scopus ID)
Funder
Swedish Research Council, 602699; 2016-2075-5.1; 2016-04519
Note

Other funding  agencies:

Deutsche Forschungsgemeinschaft (DFG): CRC1149 A01 

Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2019-08-29Bibliographically approved
Mohlin, C., Petrus-Reurer, S., Lanner, F., Sandholm, K., Kvanta, A., Nilsson, B. & Nilsson Ekdahl, K. (2017). Complement system proteins in human embryonic stem cell-derived retinal pigment epithelial cells co-cultured with or without porcine retina. Paper presented at 16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK. Molecular Immunology, 89, 162-163
Open this publication in new window or tab >>Complement system proteins in human embryonic stem cell-derived retinal pigment epithelial cells co-cultured with or without porcine retina
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2017 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, p. 162-163Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology
Research subject
Biomedical Sciences, Immunology
Identifiers
urn:nbn:se:lnu:diva-68148 (URN)10.1016/j.molimm.2017.06.132 (DOI)000410014500107 ()
Conference
16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK
Available from: 2017-10-02 Created: 2017-10-02 Last updated: 2018-11-16Bibliographically approved
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