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Särndahl, Eva
Alternative names
Publications (10 of 14) Show all publications
Bergström, I., Lundberg, A., Jönsson, S., Ernerudh, J., Särndahl, E. & Jonasson, L. (2014). Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease.
Open this publication in new window or tab >>Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

An imbalance between pro- and anti-inflammatory actions is believed to drive progression of atherosclerosis. Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of anti-inflammatory effects of glucocorticoids. Here, we investigated whether expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) was altered in patients with coronary artery disease (CAD) and also related findings to glucocorticoid sensitivity ex vivo.

We included 57 patients 6-12 months after acute coronary syndrome (ACS), 10 patients with ACS, and healthy controls. AnxA1 mRNA was measured in PBMCs and AnxA1 protein was assessed in monocytes and lymphocyte subsets by flow cytometry. In post-ACS patients and controls, glucocorticoid sensitivity was determined by measuring inhibitory effects of dexamethasone on LPS46 induced cytokine secretion.

AnxA1 mRNA levels in PBMCs were higher in patients compared with controls, although most pronounced in ACS patients. AnxA1 protein was most abundant in the monocyte fraction. ACS patients exhibited the highest levels of cell surface-associated AnxA1 protein while levels in post-ACS patients and controls were similar. Ex vivo assays showed that PBMCs from post-ACS patients were more prone to release IL-6. Glucocorticoid sensitivity correlated with cell surface-associated AnxA1 protein in peripheral monocytes. Dexamethasone also induced upregulation of AnxA1 mRNA.

AnxA1 expression in PBMCs is closely associated with glucocorticoid actions and cell surface associated AnxA1 appears to be a marker of glucocorticoid sensitivity. Although still speculative, a “normal” expression of cell surface-associated AnxA1 in post-ACS patients may suggest that glucocorticoid actions in vivo are insufficient to provide adequate anti-inflammatory effects in these patients.

Keywords
Annexin A1, monocytes, glucocorticoids, coronary artery disease, acute coronary syndrome
National Category
Cardiac and Cardiovascular Systems Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-114122 (URN)
Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2018-01-11Bibliographically approved
Bergström, I., Lundberg, A., Reutelingsperger, C., Ernerudh, J., Särndahl, E. & Jonasson, L. (2014). Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease.
Open this publication in new window or tab >>Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Increased proportions of circulating proinflammatory CD56+ T cells have been reported in patients with coronary artery disease (CAD). Yet, little is known about regulation of these cells. In the present study, we investigated the expression and potential role of the glucocorticoid-mediated protein annexin A1 (AnxA1) in CD56+ and CD56-T cell subsets, with focus on CAD.

Methods and Results: We included totally 52 healthy individuals, 28 patients with acute coronary syndrome (ACS) and 57 patients with a history of ACS. AnxA1 mRNA expression was assessed in peripheral blood mononuclear cells. AnxA1 protein expression (total and cell surface-associated) was measured by whole blood flow cytometry in circulating CD56+ and CD56- T cell subsets. Furthermore, inhibitory effects of dexamethasone and/or recombinant AnxA1 on cytokine secretion by CD56+ and CD56- T cells were explored in vitro. We found that CD56+ T cells (the majority CD8+), expressed higher levels of AnxA1 mRNA and protein than did CD56- T cells. When comparing CAD patients with healthy controls, significantly higher levels of cell surface-associated AnxA1 expression were seen in patients, most pronounced in ACS patients. In vitro, dexamethasone reduced cytokine secretion by CD56+ T cells, whereas AnxA1 alone had no effect, and AnxA1 combined with dexamethasone abolished the dexamethasone-induced suppressive effects.

Conclusion: AnxA1 was expressed more abundantly in proinflammatory CD56+ T cells. Patients with ACS exhibited increased levels of cell surface-associated AnxA1, thus indicating increased activation of the AnxA1 pathway. Our data further suggested that AnxA1 might counteract glucocorticoid mediated anti-inflammatory effects in T cells.

Keywords
Annexin A1, T cell, CD56, coronary artery disease, acute coronary syndrome
National Category
Cardiac and Cardiovascular Systems Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-114121 (URN)
Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2018-01-11Bibliographically approved
Eklund, D., Welin, A., Andersson, H., Verma, D., Söderkvist, P., Stendahl, O., . . . Lerm, M. (2014). Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis. The Journal of infectious diseases, 209(5), 749-753
Open this publication in new window or tab >>Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis
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2014 (English)In: The Journal of infectious diseases, ISSN 1537-6613, Vol. 209, no 5, p. 749-753Article in journal (Refereed) Published
Abstract [en]

Activation of the NLRP3 inflammasome and subsequent generation of IL-1β is initiated in macrophages upon recognition of several stimuli. In the present work, we show that gain-of-function gene variants of inflammasome components known to predispose individuals to inflammatory disorders have a host-protective role during infection with Mycobacterium tuberculosis. By isolation of macrophages from patients and healthy blood donors with genetic variants in NLRP3 and CARD8 and subsequently infecting the cells by virulent M. tuberculosis, we show that these gene variants, combined, are associated with increased control of bacterial growth in human macrophages.

Place, publisher, year, edition, pages
University of Chicago Press / Oxford University Press (OUP), 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-100889 (URN)10.1093/infdis/jit572 (DOI)000331873700016 ()24158955 (PubMedID)
Available from: 2013-11-14 Created: 2013-11-14 Last updated: 2015-04-10Bibliographically approved
Särndahl, E., Bergström, I., Nijm, J., Forslund, T., Perretti, M. & Jonasson, L. (2010). Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease. Metabolism: Clinical and Experimental, 59(3), 443-440
Open this publication in new window or tab >>Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease
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2010 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 59, no 3, p. 443-440Article in journal (Refereed) Published
Abstract [en]

Background: A dysregulated cortisol response in patients with stable coronary artery disease (CAD) is related to systemic inflammatory activity. Moreover, a dysfunctional activation status of neutrophils in CAD has been discussed. The anti-inflammatory actions of glucocorticoids are mediated by annexin-1 (ANXA1), a protein mainly expressed by innate immune cells. An altered expression of glucocorticoid receptors (GR) and ANXA1 has been associated with glucocorticoid resistance.

Methods and Results: Salivary cortisol levels were measured in the morning and evening during 3 consecutive days in 30 CAD patients and 30 healthy individuals. The neutrophil expression of GR and ANXA1 was determined by flow cytometry. The effect of exogenous ANXA1 was determined in neutrophil stimulation assays. The patients showed a flattened diurnal cortisol pattern compared to healthy subjects, involving higher levels in the evening. The neutrophil expression of GRtotal and GRα, as well as the ratio of GRα:GRβ expression was significantly decreased in patients, whereas the GRβ expression did not differ compared to controls. The neutrophil expression of ANXA1 was significantly increased in patients. Ex vivo, ANXA1 suppressed LTB4-induced ROS production in neutrophils from patients, but not from controls. On the other hand, ANXA1 impaired the LTB4-induced up-regulation of β2-integrins in both patients and controls.

Conclusion: CAD patients displayed a more flattened diurnal cortisol rhythm caused by higher cortisol levels in the evening compared to healthy subjects. Our findings indicate a chronic overactivation of the hypothalamic-pituitary-adrenal (HPA) axis but give no conclusive evidence for glucocorticoid resistance, as assessed by the neutrophil expression of GR and ANXA1. The data rather point towards an increased anti-inflammatory potential in neutrophils from patients with stable CAD.

Keywords
Coronary artery disease, cortisol, neutrophil, glucocorticoid receptor, annexin-1
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17247 (URN)10.1016/j.metabol.2009.07.044 (DOI)000276761800021 ()
Note
Original Publication: Eva Särndahl, Ida Bergström, Johnny Nijm, Tony Forslund, Mauro Perretti and Lena Jonasson, Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease, 2010, Metabolism: Clinical and Experimental, (59), 3, 443-440. http://dx.doi.org/10.1016/j.metabol.2009.07.044 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-03-12 Created: 2009-03-12 Last updated: 2017-12-13
Winberg Tinnerfelt, M., Holm, Å., Särndahl, E., Vinet, A. F., Descoteaux, A., Magnusson, K.-E., . . . Lerm, M. (2009). Leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts. Microbes and infection, 11(2), 215-222
Open this publication in new window or tab >>Leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts
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2009 (English)In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 11, no 2, p. 215-222Article in journal (Refereed) Published
Abstract [en]

Lipophosphoglycan (LPG), the major surface glycoconjugate on Leishmania donovani promastigotes, is crucial for the establishment of infection inside macrophages. LPG comprises a polymer of repeating Gal beta 1,4Man alpha-PO4 attached to a lysophosphatidylinositol membrane anchor. LPG is transferred from the parasite to the host macrophage membrane during phagocytosis and induces periphagosomal F-actin accumulation correlating with an inhibition of phagosomal maturation. The biophysical properties of LPG suggest that it may be intercalated into membrane rafts of the host-cell membrane. The aim of this study was to investigate if the effects of LPG on phagosomal maturation are mediated via action on membrane rafts. We show that LPG accumulates in rafts during phagocytosis of L. donovani and that disruption of membrane rafts abolished the effects of LPG on periphagosomal F-actin and phagosomal maturation, indicating that LPG requires intact membrane rafts to manipulate host-cell functions. We conclude that LPG associates with membrane rafts in the host cell and exert its actions on host-cell actin and phagosomal maturation through subversion of raft function.

Keywords
Leishmania, Lipophosphoglycan, Membrane rafts, Phagosomal maturation, Actin
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17886 (URN)10.1016/j.micinf.2008.11.007 (DOI)
Note

Original Publication: Martin Winberg Tinnerfelt, Åsa Holm, Eva Särndahl, Adrien F Vinet, Albert Descoteaux, Karl-Eric Magnusson, Birgitta Rasmusson and Maria Lerm, Leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts, 2009, MICROBES AND INFECTION, (11), 2, 215-222. http://dx.doi.org/10.1016/j.micinf.2008.11.007 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/

Available from: 2009-05-20 Created: 2009-04-24 Last updated: 2017-12-13Bibliographically approved
Welin, A., Winberg Tinnerfelt, M., Abdalla, H., Särndahl Lindblom, E., Rasmusson, B., Stendahl, O. & Lerm, M. (2008). Incorporation of Mycobacterium tuberculosis lipoarabinomannan into macrophage membrane rafts is a prerequisite for the phagosomal maturation block.. Infection and Immunity, 76(7), 2882-2887
Open this publication in new window or tab >>Incorporation of Mycobacterium tuberculosis lipoarabinomannan into macrophage membrane rafts is a prerequisite for the phagosomal maturation block.
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2008 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 76, no 7, p. 2882-2887Article in journal (Refereed) Published
Abstract [en]

Lipoarabinomannan (LAM) is one of the key virulence factors for Mycobacterium tuberculosis, the etiological agent of tuberculosis. During uptake of mycobacteria, LAM interacts with the cell membrane of the host macrophage and can be detected throughout the cell upon infection. LAM can inhibit phagosomal maturation as well as induce a proinflammatory response in bystander cells. The aim of this study was to investigate how LAM exerts its action on human macrophages. We show that LAM is incorporated into membrane rafts of the macrophage cell membrane via its glycosylphosphatidylinositol anchor and that incorporation of mannose-capped LAM from M. tuberculosis results in reduced phagosomal maturation. This is dependent on successful insertion of the glycosylphosphatidylinositol anchor. LAM does not, however, induce the phagosomal maturation block through activation of p38 mitogen-activated protein kinase, contradicting some previous suggestions.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-20816 (URN)10.1128/IAI.01549-07 (DOI)18426888 (PubMedID)
Available from: 2009-09-22 Created: 2009-09-22 Last updated: 2018-01-13Bibliographically approved
Särndahl, E., Bergström, I., Brodin Patcha, V., Nijm, J., Setterud, H. & Jonasson, L. (2007). Activation state of neutrophils in patients with stable coronary artery disease. In: 76th Congress of the European Atherosclerosis Society,2007.
Open this publication in new window or tab >>Activation state of neutrophils in patients with stable coronary artery disease
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2007 (English)In: 76th Congress of the European Atherosclerosis Society,2007, 2007Conference paper, Published paper (Other academic)
Abstract [en]

   

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-40760 (URN)54061 (Local ID)54061 (Archive number)54061 (OAI)
Available from: 2009-10-10 Created: 2009-10-10
Lerm, M., Brodin Patcha, V., Ruishalme, I., Stendahl, O. & Särndahl, E. (2007). Inactivation of Cdc42 is nessecary for depolymerization of phagosomal F-actin and subsequent phagosomal maturation. Journal of Immunology, 178(11), 7357-7365
Open this publication in new window or tab >>Inactivation of Cdc42 is nessecary for depolymerization of phagosomal F-actin and subsequent phagosomal maturation
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2007 (English)In: Journal of Immunology, ISSN 0022-1767, Vol. 178, no 11, p. 7357-7365Article in journal (Refereed) Published
Abstract [en]

Phagocytosis is a complex process involving the activation of various signaling pathways, such as the Rho GTPases, and the subsequent reorganization of the actin cytoskeleton. In neutrophils, Rac and Cdc42 are activated during phagocytosis but less is known about the involvement of these GTPases during the different stages of the phagocytic process. The aim of this study was to elucidate the role of Cdc42 in phagocytosis and the subsequent phagosomal maturation. Using a TAT-based protein transduction technique, we introduced dominant negative and constitutively active forms of Cdc42 into neutrophil-like HL60 (human leukemia) cells that were allowed to phagocytose IgG-opsonized yeast particles. Staining of cellular F-actin in cells transduced with constitutively active Cdc42 revealed that the activation of Cdc42 induced sustained accumulation of periphagosomal actin. Moreover, the fusion of azurophilic granules with the phagosomal membrane was prevented by the accumulated F-actin. In contrast, introducing dominant negative Cdc42 impaired the translocation per se of azurophilic granules to the periphagosomal area. These results show that efficient phagosomal maturation and the subsequent eradication of ingested microbes in human neutrophils is dependent on a strictly regulated Cdc42. To induce granule translocation, Cdc42 must be in its active state but has to be inactivated to allow depolymerization of the F-actin cage around the phagosome, a process essential for phagolysosome formation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14632 (URN)
Available from: 2007-09-13 Created: 2007-09-13
Särndahl, E., Bergström, I., Brodin, V. P., Nijm, J., Lundqvist Setterud, H. & Jonasson, L. (2007). Neutrophil activation status in stable coronary artery disease.. PLoS ONE, 2(10), e1056-
Open this publication in new window or tab >>Neutrophil activation status in stable coronary artery disease.
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2007 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 2, no 10, p. e1056-Article in journal (Refereed) Published
Abstract [en]

Background: During the last years, neutrophils have emerged as important players in atherogenesis. They are highly activated in peripheral blood of patients with unstable angina. Moreover, a primed state of circulating neutrophils has been proposed in patients with stable angina. Our aim was to investigate the neutrophil activation status in patients with stable coronary artery disease (CAD) at conventional drug treatment.

Methodology and principal findings: Thirty patients with stable CAD and 30 healthy controls were included using a paired design. The neutrophil expression of CD18 and high-affinity state of CD11b was analysed by flow cytometry before and after stimulation with chemoattractants. Also, the production of reactive oxygen species (ROS) was determined by chemiluminescence. During basal conditions, the neutrophil expression of CD18 or high-affinity state of CD11b did not differ between patients and controls. Chemoattractants (Interleukin-8 and Leukotriene B(4)) did not increase either the expression or the amount of high-affinity CD11b/CD18-integrins in CAD patients compared to controls, and had no effect on the production of ROS. On the other hand, the ROS production in response to C3bi-opsonised yeast particles and the neutrophils' inherent capacity to produce ROS were both significantly decreased in patients.

Conclusion/Significance: We could not find any evidence that neutrophils in patients with stable CAD were primed, i.e. more prone to activation, compared to cells from healthy controls. According to our data, the circulating neutrophils in CAD patients rather showed an impaired activation status. It remains to be elucidated whether the neutrophil dysfunction in CAD is mainly a marker of chronic disease, an atherogenic factor or a consequence of the drug treatment.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17246 (URN)10.1371/journal.pone.0001056 (DOI)17957240 (PubMedID)
Available from: 2009-03-12 Created: 2009-03-12 Last updated: 2010-01-14
Lerm, M., Holm, Å., Seiron, Å., Särndahl, E., Magnusson, K.-E. & Rasmusson, B. (2006). Leishmania donovani requires functional Cdc42 and Rac1 to prevent phagosomal maturation. Infection and Immunity, 74(5), 2613-2618
Open this publication in new window or tab >>Leishmania donovani requires functional Cdc42 and Rac1 to prevent phagosomal maturation
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2006 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 74, no 5, p. 2613-2618Article in journal (Refereed) Published
Abstract [en]

Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase Cα. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation. Copyright © 2006, American Society for Microbiology. All Rights Reserved.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-35218 (URN)10.1128/IAI.74.5.2613-2618.2006 (DOI)25767 (Local ID)25767 (Archive number)25767 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
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