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

Direct link
BETA
Håkansson, Lena
Alternative names
Publications (10 of 25) Show all publications
Blom, K., ElShafie, A. I., Jönsson, U.-B., Rönnelid, J., Håkansson, L. & Venge, P. (2018). The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 126(1), 85-91
Open this publication in new window or tab >>The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis
Show others...
2018 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 1, p. 85-91Article in journal (Refereed) Published
Abstract [en]

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. Recent findings indicate that dendritic cells have a key role in the defense against the Leishmania parasite and that the activity of this cell may be modified by the eosinophil secretory protein eosinophil-derived neurotoxin (EDN). We hypothesized that the interactions between dendritic cells and EDN might be of importance in the disease development. Cellular content of EDN was analyzed by ELISA. The single-nucleotide polymorphisms at positions 405, 416, and 1122 in the EDN gene were analyzed by real-time PCR with TaqMan((R)) reagents. The study cohorts comprised 239 Sudanese subjects (65 healthy controls and 174 with VL) and 300 healthy Swedish controls. The eosinophil content of EDN was lower in VL as compared with controls (p < 0.0001). The EDN405 (G>C) genotype distribution was similar among Swedish and Sudanese controls, whereas VL subjects had a higher prevalence of the EDN405-GG genotype (p < 0.0001). The content of EDN in the eosinophils was closely linked to the EDN405 polymorphism (p = 0.0002). Our findings suggest that the predisposition to acquire VL is related to the genetic polymorphism of the EDN gene and the reduced production by the eosinophil of this gene product.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
Visceral leishmaniasis, kala-azar, eosinophil granulocyte, polymorphism, RNASE2
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-338960 (URN)10.1111/apm.12780 (DOI)000418846700011 ()29193305 (PubMedID)
Available from: 2018-01-18 Created: 2018-01-18 Last updated: 2018-02-27Bibliographically approved
Stålhammar, M. E., Douhan Håkansson, L. & Sindelar, R. (2017). Bacterial N-formyl Peptides Reduce PMA and Escherichia coli-Induced Neutrophil Respiratory Burst in Term Neonates and Adults. Scandinavian Journal of Immunology, 85(5), 365-371
Open this publication in new window or tab >>Bacterial N-formyl Peptides Reduce PMA and Escherichia coli-Induced Neutrophil Respiratory Burst in Term Neonates and Adults
2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 85, no 5, p. 365-371Article in journal (Refereed) Published
Abstract [en]

Neutrophil migration and respiratory burst is the prerequisite for efficient first line defense against invading microorganisms. However, migration and respiratory burst can be compromised in adults and especially in newborn infants, where sustained neutrophil accumulation, uncontrolled burst and reduced scavenging of ROS might cause inadvertent tissue damage due to uncontrolled inflammation. The aim of this study was to investigate the modulatory effect of the chemoattractants formyl-methionyl-leucyl-phenylalanine (fMLP) and IL-8 on respiratory burst in neutrophils from term newborn infants and adults. Whole blood from the umbilical cord of 17 healthy term newborn infants delivered by caesarean section and from 17 healthy adults as reference was preincubated with fMLP or IL-8 and stimulated with PMA or E.coli bacteria. Respiratory burst was quantified by flow cytometry analysis of dihydrorhodamine 123 fluorescence. fMLP reduced the PMA-induced respiratory burst of neutrophils from newborn infants and adults by 12% and 21% respectively (p<0.05). E.coli-induced burst was also reduced by fMLP in neutrophils from newborn infants (10%; p<0.01) and adults (6%; p<0.05). No such changes were observed with IL-8. Similar respiratory burst in response to single stimulus with PMA or E.coli were observed in both newborn infants and adults. fMLP reduced PMA- and E.coli-induced respiratory burst of neutrophils in whole blood from term newborn infants as well as in adults. The reduced respiratory burst by fMLP might be a mechanism to reduce the detrimental effects of uncontrolled inflammation during neutrophil migration

National Category
Immunology in the medical area
Research subject
Immunology; Pediatrics
Identifiers
urn:nbn:se:uu:diva-214732 (URN)10.1111/sji.12537 (DOI)000400011500006 ()28199745 (PubMedID)
Note

Title in Dissertation reference list: Bacterial N-formyl Peptides Reduce PMA and E.coli Induced Neutrophil Respiratory Burst in Term Neonates and Adults.

Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2018-01-11Bibliographically approved
Stålhammar, M., Håkansson, L. D., Jonzon, A. & Sindelar, R. (2017). Differential Neutrophil Chemotactic Response towards IL-8 and Bacterial N-formyl Peptides in Term Newborn Infants. Upsala Journal of Medical Sciences, 122(1), 35-42
Open this publication in new window or tab >>Differential Neutrophil Chemotactic Response towards IL-8 and Bacterial N-formyl Peptides in Term Newborn Infants
2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 35-42Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A prerequisite for an effective innate immunity is the migrative ability of neutrophils to respond to inflammatory and infectious agents such as the intermediate interleukin (IL)-8 and the end-target formyl-methionyl-leucyl-phenylalanine (fMLP) chemoattractants. The aim was to study the chemotactic capacity of neutrophils from newborn infants and adults in response to IL-8 and the bacterial peptide fMLP.

METHODS: In the under-agarose cell migration assay, isolated leukocytes from healthy adults and from cord blood of healthy term newborn infants were studied with dose responses towards IL-8 and fMLP. The same number of leukocytes (1 × 10(5) cells), with the same distribution of neutrophils and monocytes, were analyzed in neonates and adults. Chemotaxis was distinguished from randomly migrating neutrophils, and the neutrophil pattern of migration, i.e. the migration distance and the number of migrating neutrophils per distance, was evaluated.

RESULTS: In comparison to adults, fewer neutrophils from newborn infants migrated towards IL-8 and for a shorter distance (P < .01, respectively). The number of neutrophils migrating to different gradients of fMLP, the distance they migrated, and the correlation between the number and the distance were the same for neonates and adults. Random migration did not differ in any instance.

CONCLUSION: Chemotaxis of neutrophils from newborn infants was as co-ordinated as neutrophils from adults in response to fMLP, whereas the response to IL-8 was reduced. The differential response of neutrophils from neonates to intermediate and end-target chemoattractants could indicate a reduced infectious response.

Keywords
Chemotaxis, chemoattractants, fMLP, innate immunity, IL-8, neutrophils, newborn infants
National Category
Pediatrics Immunology in the medical area
Research subject
Immunology; Pediatrics
Identifiers
urn:nbn:se:uu:diva-304756 (URN)10.1080/03009734.2016.1228721 (DOI)000396476600005 ()27690722 (PubMedID)
Available from: 2016-10-10 Created: 2016-10-10 Last updated: 2018-01-14Bibliographically approved
Venge, P., Eriksson, A.-K., Douhan Håkansson, L. & Pauksen, K. (2017). Human Neutrophil Lipocalin in Activated Whole Blood Is a Specific and Rapid Diagnostic Biomarker of Bacterial Infections in the Respiratory Tract. Clinical and Vaccine Immunology, 24(7), Article ID UNSP e00064.
Open this publication in new window or tab >>Human Neutrophil Lipocalin in Activated Whole Blood Is a Specific and Rapid Diagnostic Biomarker of Bacterial Infections in the Respiratory Tract
2017 (English)In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 24, no 7, article id UNSP e00064Article in journal (Refereed) Published
Abstract [en]

The distinction between bacterial and viral causes of infections of the respiratory tract is a major but important clinical challenge. We investigated the diagnostic performance of human neutrophil lipocalin (HNL) in respiratory tract infections compared to those of C-reactive protein (CRP) and procalcitonin (PCT). Patients were recruited from the emergency department and from a primary care unit (n = 162). The clinical diagnosis with regard to bacterial or viral cause of infection was complemented with objective microbiological/serological testing. HNL was measured in whole blood after preactivation with the neutrophil activator formyl-methionine-leucine-phenylalanine (fMLP) (B-HNL), and CRP and PCT were measured in plasma. Head-to-head comparisons of the three biomarkers showed that B-HNL was a superior diagnostic means to distinguish between causes of infections, with areas under the concentration-time curve (AUCs) of receiver operating characteristic (ROC) analysis for HNL of 0.91 (95% confidence interval [CI], 0.83 to 0.96) and 0.92 (95% CI, 0.82 to 0.97) for all respiratory infections and for upper respiratory infections, respectively, compared to 0.72 (95% CI, 0.63 to 0.80) and 0.68 (95% CI, 0.56 to 0.79) for CRP, respectively (P = 0.001). In relation to major clinical symptoms of respiratory tract infections (cough, sore throat, stuffy nose, and signs of sinusitis), AUCs varied between 0.88 and 0.93 in those patients with likely etiology (i.e., etiology is likely determined) of infection, compared to 0.63 and 0.71 for CRP, respectively, and nonsignificant AUCs for PCT. The diagnostic performance of B-HNL is superior to that of plasma CRP (P-CRP) and plasma PCT (P-PCT) in respiratory tract infections, and the activity specifically reflects bacterial challenge in the body. The rapid and accurate analysis of HNL by point-of-care technologies should be a major advancement in the diagnosis and management of respiratory infections with respect to antibiotic treatment.

Keywords
antibiotic resistance, biomarker, lipocalin, point of care, respiratory infection
National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-330026 (URN)10.1128/CVI.00064-17 (DOI)000404927700006 ()
Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2017-10-31Bibliographically approved
Stålhammar, M., Sindelar, R. & Douhan Håkansson, L. (2016). Neutrophil Receptor Response to Bacterial N-formyl Peptides is Similar in Term Newborn Infants and Adults in Contrast to IL-8. Scandinavian Journal of Immunology, 84(6), 332-337
Open this publication in new window or tab >>Neutrophil Receptor Response to Bacterial N-formyl Peptides is Similar in Term Newborn Infants and Adults in Contrast to IL-8
2016 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 84, no 6, p. 332-337Article in journal (Refereed) Published
Abstract [en]

We have previously observed that neutrophils from neonates exhibit different migratory responses to intermediate and end-target chemoattractants compared to adults. The aim of the present study was to investigate the effect of the chemoattractants IL-8 (intermediate) and formyl-methionine-leucyl-phenylalanine (fMLP; end-target) on cell surface receptor expression involved in adhesion, migration and granule release of neutrophils from term newborn infants and adults. Heparinized cord blood from 16 healthy term infants delivered by caesarean section and peripheral blood from 17 healthy adults were incubated with 1 μM IL-8 or 0.01 μM fMLP, previously defined as optimal inducers of neutrophil migration. The leukocytes were labelled with antibodies to cell surface receptors (CD11b, CD15S, CD18, CD35, CD44, CD64, CD65, CD88, CD162, CD181 and CD182). Receptor expression was quantified by flow cytometry analysis. Up regulation of CD11b and down regulation of CD88 and CD182 after stimulation with IL-8, was more pronounced in adults than in neonates (p<0.05, p<0.05 and p≤0.001 respectively), whereas fMLP induced changes in receptor expression that were of the same magnitude in neutrophils from neonates as from adults. We observed similar expression of receptors that mediate adhesion, migration, granule activation, and phagocytosis induced by fMLP in neutrophils from neonates and adults. In contrast, differences between neonates and adults, induced by IL-8, suggest that the neutrophil response to intermediate chemoattractants might lead to a compromised infectious response in newborn infants.

Keywords
neutrophils, cell surface molecules, term newborn infants, IL-8, fMLP
National Category
Immunology in the medical area
Research subject
Immunology; Pediatrics
Identifiers
urn:nbn:se:uu:diva-304757 (URN)10.1111/sji.12477 (DOI)000393285400005 ()27606963 (PubMedID)
Available from: 2016-10-10 Created: 2016-10-10 Last updated: 2018-01-14Bibliographically approved
Manivel, V. A., Sohrabian, A., Wick, M. C., Mullazehi, M., Håkansson, L. D. & Rönnelid, J. (2015). Anti-type II collagen immune complex-induced granulocyte reactivity is associated with joint erosions in RA patients with anti-collagen antibodies. Arthritis Research & Therapy, 17, Article ID 8.
Open this publication in new window or tab >>Anti-type II collagen immune complex-induced granulocyte reactivity is associated with joint erosions in RA patients with anti-collagen antibodies
Show others...
2015 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, article id 8Article in journal (Refereed) Published
Abstract [en]

Introduction: Rheumatoid arthritis (RA) patients with autoantibodies against collagen type II (CII) are characterized by acute RA onset with elevated inflammatory measures and early joint erosions as well as increased production of tumor necrosis factor-alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMC) stimulated by anti-CII immune complexes (IC) in vitro. Polymorphonuclear granulocytes (PMN) are abundant in RA synovial fluids, where they might interact directly with anti-CII IC in the articular cartilage, but no studies have investigated PMN responses towards anti-CII IC. The aim was to investigate whether PMN react towards anti-CII IC, and to what extent such reactivity might relate to the clinical acute onset RA phenotype associated with elevated levels of anti-CII. Methods: PMN and PBMC isolated from healthy donors were stimulated with IC made with a set of 72 baseline patient sera (24 anti-CII positive, 48 anti-CII negative) chosen from a clinically well-characterized RA cohort with two-year radiological follow-up with Larsen scoring. PMN expression of cluster of differentiation (CD) 11b, CD66b, CD16 and CD32 was measured by flow cytometry, whereas PMN production of myeloperoxidase (MPO) and interleukin (IL)-17, and PBMC production of TNF-alpha was measured with enzyme linked immunosorbent assay. Results: PMN expression of CD11b, CD66b and MPO, and PBMC production of TNF-alpha were upregulated whereas PMN expression of CD16 and CD32 were downregulated by anti-CII IC. CD16, CD66b, and MPO production correlated to serum anti-CII levels (Spearman's rho = 0.315, 0.675 and 0.253, respectively). CD16 was associated with early joint erosions (P = 0.024, 0.034, 0.046 at baseline, one and two years) and CD66b was associated with changes in joint erosions (P = 0.017 and 0.016, at one and two years compared to baseline, respectively). CD66b was associated with baseline C-reactive protein and PBMC production of TNF-alpha was associated with baseline erythrocyte sedimentation rate, in accordance with our earlier findings. No clinical associations were observed for MPO or IL-17. Conclusion: PMN responses against anti-CII IC are more closely associated with early joint erosions than are PBMC cytokine responses. PMN reactivity against anti-CII IC may contribute to joint destruction in newly diagnosed RA patients with high levels of anti-CII.

National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-251853 (URN)10.1186/s13075-015-0523-7 (DOI)000351573200001 ()25598326 (PubMedID)
Available from: 2015-04-28 Created: 2015-04-24 Last updated: 2018-02-27Bibliographically approved
Venge, P., Douhan Håkansson, L., Garwicz, D., Peterson, C., Xu, S. & Pauksen, K. (2015). Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections. Clinical and Vaccine Immunology, 22(9), 1025-1032
Open this publication in new window or tab >>Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections
Show others...
2015 (English)In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 22, no 9, p. 1025-1032Article in journal (Refereed) Published
Abstract [en]

The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P<0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P<0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-263440 (URN)10.1128/CVI.00347-15 (DOI)000360491000006 ()26135974 (PubMedID)
Available from: 2015-10-07 Created: 2015-09-30 Last updated: 2018-01-11Bibliographically approved
Venge, P., Douhan, L. H., Garwicz, D., Peterson, C., Xu, S. & Pauksen, K. (2015). Human neutrophil lipocalin in fMLP-activated whole blood as a diagnostic means to distinguish between acute bacterial and viral infections. JIM - Journal of Immunological Methods, 424, 85-90
Open this publication in new window or tab >>Human neutrophil lipocalin in fMLP-activated whole blood as a diagnostic means to distinguish between acute bacterial and viral infections
Show others...
2015 (English)In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 424, p. 85-90Article in journal (Refereed) Published
Abstract [en]

The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) in serum distinguishes acute infections with high accuracy, but in the emergency setting the assay time should be <15-20 min, which excludes the use of serum samples. The aim was therefore to develop a novel rapid assay principle and test its clinical performance. Methods: Serum and neutrophils obtained from 84 infected and 20 healthy subjects were used in the experimental study. 725 subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the clinical study. HNL was measured in EDTA-plasma by ELISA or in heparinized whole blood after fMLP activation by a prototype point-of-care assay. Results: Increased release of HNL from neutrophils after activation with fMLP was seen already after 5 min incubation. The release of HNL from purified neutrophils after 15 min incubation with fMLP was significantly correlated to the HNL concentrations in serum obtained from the same patient (r = 0.74, p < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the ROC-curves were 0.95 (95% CI 0.91-0.97) and 0.88 (95% CI 0.84-0.91) for HNL in fMLP-activated whole blood and EDTA-plasma, respectively, (p <0.001) and in the distinction between bacterial and viral infections 0.91 (95% CI 0.86-0.95) and 0.76 (95% CI 0.70-0.81), respectively (p <0.001). Conclusion: The clinical performance of HNL in fMLP-activated whole blood was superior to HNL in EDTA-plasma and similar to HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

Keywords
Acute infection, Neutrophil, Bacterial infection, Viral infection, Point-of-care, Human neutrophil lipocalin
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-265624 (URN)10.1016/j.jim.2015.05.004 (DOI)000361848900011 ()26002155 (PubMedID)
Available from: 2015-11-04 Created: 2015-11-02 Last updated: 2018-01-10Bibliographically approved
Eriksson, O., Håkansson, L. D., Karawajczyk, M. & Garwicz, D. (2015). Neutrophil CD64 expression - comparison of two different flow cytometry protocols on EPICs MCL and the Leuko64 (TM) assay on a Celldyn Sapphire haematology analyser. Scandinavian Journal of Clinical and Laboratory Investigation, 75(5), 428-433
Open this publication in new window or tab >>Neutrophil CD64 expression - comparison of two different flow cytometry protocols on EPICs MCL and the Leuko64 (TM) assay on a Celldyn Sapphire haematology analyser
2015 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 75, no 5, p. 428-433Article in journal (Refereed) Published
Abstract [en]

Objective. To evaluate the Trillium Diagnostics Leuko64 (TM) assay on Abbott Celldyn Sapphire haematology analyser compared to two flow cytometry protocols on Beckman Coulter EPICS MCL flow cytometer. Materials and methods. CD64 expression on neutrophils was determined by two flow cytometry protocols and by a commercial assay on an automatic haematology analyser. The inclusion of study subjects was based on elevated procalcitonin (PCT) values, identifying patients where a systemic infection was suspected. Healthy blood donors were used as a reference group. Results. Statistically significant correlations between the Trillium Diagnostics Leuko64 (TM) assay and the flow cytometry methods were found when measuring neutrophil CD64 expression. Conclusions. The good correlation between a reference method and an automated haematology analyser method for CD64 expression on neutrophils supports introduction of the latter assay for routine use as an independent biomarker of bacterial infection and inflammation.

Keywords
CD64, flow cytometry, neutrophils, method comparison
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-262972 (URN)10.3109/00365513.2015.1031690 (DOI)000360177600012 ()25874478 (PubMedID)
Available from: 2015-09-23 Created: 2015-09-23 Last updated: 2017-12-01Bibliographically approved
Vahlquist, A., Håkansson, L. D., Rönnblom, L., Karawajczyk, M., Fasth, A., van Gijn, M. E., . . . Venge, P. (2015). Recurrent Pyoderma Gangrenosum and Cystic Acne Associated with Leucocyte Adhesion Deficiency due to Novel Mutations in ITGB2: Successful Treatment with Infliximab and Adalimumab. Acta Dermato-Venereologica, 95(3), 349-351
Open this publication in new window or tab >>Recurrent Pyoderma Gangrenosum and Cystic Acne Associated with Leucocyte Adhesion Deficiency due to Novel Mutations in ITGB2: Successful Treatment with Infliximab and Adalimumab
Show others...
2015 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 3, p. 349-351Article in journal (Refereed) Published
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-251855 (URN)10.2340/00015555-1929 (DOI)000351249600022 ()
Available from: 2015-04-28 Created: 2015-04-24 Last updated: 2017-12-04Bibliographically approved
Organisations

Search in DiVA

Show all publications