lnu.sePublikationer
Ändra sökning
Länk till posten
Permanent länk

Direktlänk
BETA
Alternativa namn
Publikationer (10 of 46) Visa alla publikationer
Thorgersen, E. B., Barratt-Due, A., Haugaa, H., Harboe, M., Pischke, S. E., Nilsson, P. H. & Mollnes, T. E. (2019). The Role of Complement in Liver Injury, Regeneration, and Transplantation. Hepatology
Öppna denna publikation i ny flik eller fönster >>The Role of Complement in Liver Injury, Regeneration, and Transplantation
Visa övriga...
2019 (Engelska)Ingår i: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350Artikel i tidskrift (Refereegranskat) Epub ahead of print
Abstract [en]

The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells such as Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that likely makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation, and regeneration. Notably, complement is a double-edged sword as activation is detrimental by inducing inflammatory tissue damage in, for example, ischemia-reperfusion injury and transplant rejection yet is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings, including liver injury and regeneration after major surgery and preservation of the organ during transplantation.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2019
Nationell ämneskategori
Gastroenterologi
Forskningsämne
Naturvetenskap, Medicin
Identifikatorer
urn:nbn:se:lnu:diva-87059 (URN)10.1002/hep.30508 (DOI)000476407000001 ()30653682 (PubMedID)
Tillgänglig från: 2019-08-01 Skapad: 2019-08-01 Senast uppdaterad: 2019-08-01
Thomas, A. M., Gerogianni, A., Barratt-Due, A., McAdam, M. B., Mollnes, T. E. & Nilsson, P. H. (2018). Complement (C5)-inhibition attenuates heme-induced inflammation in human whole blood. Paper presented at 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, NM. Molecular Immunology, 102, 220-220
Öppna denna publikation i ny flik eller fönster >>Complement (C5)-inhibition attenuates heme-induced inflammation in human whole blood
Visa övriga...
2018 (Engelska)Ingår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, s. 220-220Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Ort, förlag, år, upplaga, sidor
Elsevier, 2018
Nyckelord
Complement, Heme, Inflammation, Thromboinflammation, Complement 5
Nationell ämneskategori
Immunologi
Forskningsämne
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-78411 (URN)10.1016/j.molimm.2018.06.228 (DOI)000445313600224 ()
Konferens
27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, NM
Tillgänglig från: 2018-10-22 Skapad: 2018-10-22 Senast uppdaterad: 2018-11-16Bibliografiskt granskad
Orrem, H. L., Nilsson, P. H., Pischke, S. E., Kleveland, O., Yndestad, A., Ekholt, K., . . . Mollnes, T. E. (2018). IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction. Frontiers in Immunology, 9, Article ID 2035.
Öppna denna publikation i ny flik eller fönster >>IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction
Visa övriga...
2018 (Engelska)Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, artikel-id 2035Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the anaphylatoxin receptors in whole blood from non-ST-elevation myocardial infarction (NSTEMI) patients. Separately, anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated. Materials and Methods: NSTEMI patients were randomized to one dose of tocilizumab (n = 28) or placebo (n = 32) and observed for 6 months. Whole blood samples drawn at inclusion, at day 2, 3 and after 6 months were used for mRNA isolation. Plasma was prepared for analysis of complement activation measured as sC5b-9 by ELISA. Furthermore, patients with different CAD entities comprising stable angina pectoris (SAP, n = 22), non-ST-elevation acute coronary syndrome (NSTE-ACS, n = 21) and ST-elevation myocardial infarction (STEMI, n = 20) were included. PBMC was isolated from blood samples obtained at admission to hospital and mRNA isolated. Anaphylatoxin-receptor-expression was analyzed with qPCR using mRNA from whole blood and PBMC, respectively. Results: Our main findings were (i) Tocilizumab decreased C5aR1 and C5aR2 mRNA expression significantly (p < 0.001) and substantially (> 50%) at day 2 and 3, whereas C3aR expression was unaffected. (ii) Tocilizumab did not affect complement activation. (iii) In analyzes of different CAD entities, C5aR1 expression was significantly increased in all CAD subgroups compared to controls with the highest level in the STEMI patients (p < 0.001). For C5aR2 and C3aR the expression compared to controls were more moderate with increased expression of C5aR2 in the STEMI group (p < 0.05) and C3aR in the NSTE-ACS group (p < 0.05). Conclusion: Expression of C5aR1 and C5aR2 in whole blood was significantly attenuated by IL-6R-inhibition in NSTEMI patients. These receptors were significantly upregulated in PBMC CAD patients with particularly high levels of C5aR1 in STEMI patients.

Ort, förlag, år, upplaga, sidor
Frontiers Media S.A., 2018
Nyckelord
complement, C5a receptors, C3a receptor, IL-6, myocardial infarction, inflammation
Nationell ämneskategori
Immunologi
Forskningsämne
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-78097 (URN)10.3389/fimmu.2018.02035 (DOI)000444419300001 ()2-s2.0-85053134350 (Scopus ID)
Tillgänglig från: 2018-10-01 Skapad: 2018-10-01 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
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)
Öppna denna publikation i ny flik eller fönster >>Is the polarized secretion of complement factor H of importance in age-related macular degeneration?
Visa övriga...
2018 (Engelska)Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 9Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Ort, förlag, år, upplaga, sidor
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018
Nationell ämneskategori
Oftalmologi
Forskningsämne
Naturvetenskap, Optometri
Identifikatorer
urn:nbn:se:lnu:diva-78425 (URN)000442932806149 ()
Konferens
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Tillgänglig från: 2018-10-22 Skapad: 2018-10-22 Senast uppdaterad: 2018-11-16Bibliografiskt granskad
Orrem, H. L., Shetelig, C., Ueland, T., Limalanathan, S., Nilsson, P. H., Husebye, T., . . . Yndestad, A. (2018). Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction. International Journal of Cardiology, 268, 187-192
Öppna denna publikation i ny flik eller fönster >>Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction
Visa övriga...
2018 (Engelska)Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 268, s. 187-192Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1 alpha and IL-1 beta are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. Methods: Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n=65). Results: IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. Conclusion: Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI. (C 18 Elsevier B.V. All rights reserved.

Ort, förlag, år, upplaga, sidor
Elsevier, 2018
Nyckelord
Inflammation, Cytokine, Interleukin-1, Acute coronary syndromes, Myocardial infarction, Ventricular remodelling
Nationell ämneskategori
Biokemi och molekylärbiologi
Forskningsämne
Naturvetenskap, Biomedicinsk vetenskap; Kemi, Biokemi
Identifikatorer
urn:nbn:se:lnu:diva-77369 (URN)10.1016/j.ijcard.2018.05.032 (DOI)000439363400045 ()29853279 (PubMedID)2-s2.0-85047477899 (Scopus ID)
Tillgänglig från: 2018-08-30 Skapad: 2018-08-30 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
Wibroe, P. P., Anselmo, A. C., Nilsson, P. H., Sarode, A., Gupta, V., Urbanics, R., . . . Moghimi, S. M. (2017). Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes.. Nature Nanotechnology, 12(6), 589-594
Öppna denna publikation i ny flik eller fönster >>Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes.
Visa övriga...
2017 (Engelska)Ingår i: Nature Nanotechnology, ISSN 1748-3387, E-ISSN 1748-3395, Vol. 12, nr 6, s. 589-594Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by macrophages within the first few minutes of injection overcomes adverse reactions in pigs using two independent approaches. First, we changed the particle geometry from a spherical shape (which triggers cardiopulmonary distress) to either rod- or disk-shape morphology. Second, we physically adhered spheres to the surface of erythrocytes. These strategies, which are distinct from commonly leveraged stealth engineering approaches such as nanoparticle surface functionalization with poly(ethylene glycol) and/or immunological modulators, prevent robust macrophage recognition, resulting in the reduction or mitigation of adverse cardiopulmonary distress associated with nanopharmaceutical administration.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2017
Nationell ämneskategori
Immunologi
Forskningsämne
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-65207 (URN)10.1038/nnano.2017.47 (DOI)000402769100019 ()28396605 (PubMedID)2-s2.0-85017261848 (Scopus ID)
Tillgänglig från: 2017-06-12 Skapad: 2017-06-12 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
Nilsson, P. H., Johnson, C., Pischke, S. E., Fure, H., Landsem, A., Bergseth, G., . . . Mollnes, T. E. (2017). Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation. Paper presented at 16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK. Molecular Immunology, 89, 136-137
Öppna denna publikation i ny flik eller fönster >>Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation
Visa övriga...
2017 (Engelska)Ingår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, s. 136-137Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Nationell ämneskategori
Immunologi
Forskningsämne
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-68146 (URN)10.1016/j.molimm.2017.06.075 (DOI)000410014500056 ()
Konferens
16th European Meeting on Complement in Human Disease (EMCHD), SEP 08-12, 2017, Copenhagen, DENMARK
Tillgänglig från: 2017-10-02 Skapad: 2017-10-02 Senast uppdaterad: 2018-11-16Bibliografiskt granskad
Nilsson, P. H., Johnson, C., Pischke, S. E., Fure, H., Landsem, A., Bergseth, G., . . . Mollnes, T. E. (2017). Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation. Paper presented at 16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8th-12th 2017. Molecular Immunology, 89(SI: EMCHD2017), 136-137
Öppna denna publikation i ny flik eller fönster >>Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation
Visa övriga...
2017 (Engelska)Ingår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, nr SI: EMCHD2017, s. 136-137Artikel i tidskrift, Meeting abstract (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
Elsevier, 2017
Nationell ämneskategori
Immunologi inom det medicinska området
Forskningsämne
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-73372 (URN)10.1016/j.molimm.2017.06.075 (DOI)
Konferens
16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8th-12th 2017
Tillgänglig från: 2018-04-23 Skapad: 2018-04-23 Senast uppdaterad: 2019-05-20Bibliografiskt granskad
Thomas, A. M., Schjalm, C., Nilsson, P. H., Lindenskov, P. H., Rørtveit, R., Solberg, R., . . . Barratt-Due, A. (2017). Combined inhibition of C5 and CD14 attenuates systemic inflammation in a newborn pig-model of meconium aspiration syndrome. Paper presented at 16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8th-12th 2017. Molecular Immunology, 89(SI: EMCHD2017), 166-167
Öppna denna publikation i ny flik eller fönster >>Combined inhibition of C5 and CD14 attenuates systemic inflammation in a newborn pig-model of meconium aspiration syndrome
Visa övriga...
2017 (Engelska)Ingår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, nr SI: EMCHD2017, s. 166-167Artikel i tidskrift, Meeting abstract (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
Elsevier, 2017
Nationell ämneskategori
Immunologi
Forskningsämne
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-73374 (URN)10.1016/j.molimm.2017.06.140 (DOI)
Konferens
16th European Meeting of Complement in Human Disease, Copenhagen, Denmark, September 8th-12th 2017
Tillgänglig från: 2018-04-23 Skapad: 2018-04-23 Senast uppdaterad: 2018-04-24Bibliografiskt granskad
Mahmoudi, M., Nilsson, P. H., Mollnes, T. E., Roos, D. & Sullivan, K. E. (2017). Complement Deficiencies (2nded.). In: Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D (Ed.), Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management (pp. 437-460). Berlin, Heidelberg: Springer
Öppna denna publikation i ny flik eller fönster >>Complement Deficiencies
Visa övriga...
2017 (Engelska)Ingår i: Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management / [ed] Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D, Berlin, Heidelberg: Springer, 2017, 2nd, s. 437-460Kapitel i bok, del av antologi (Refereegranskat)
Ort, förlag, år, upplaga, sidor
Berlin, Heidelberg: Springer, 2017 Upplaga: 2nd
Nationell ämneskategori
Immunologi inom det medicinska området
Forskningsämne
Biomedicinsk vetenskap, Immunologi
Identifikatorer
urn:nbn:se:lnu:diva-60983 (URN)10.1007/978-3-662-52909-6_8 (DOI)9783662529096 (ISBN)9783662529072 (ISBN)
Tillgänglig från: 2017-02-27 Skapad: 2017-02-27 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0002-7192-5794

Sök vidare i DiVA

Visa alla publikationer