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Article ; Online: The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations.

Munksgaard, Peter Svenssen / Blaakaer, Jan

2012 Volume 124, Issue 1, Page(s) 164–169

Abstract: Objective: This article represents a review of histologic and genetic findings in endometriosis and describes the mechanisms whereby genetic and non-genetic factors potentially contribute to the neoplastic progression of endometriosis.: Methods: ... ...

Abstract	Objective: This article represents a review of histologic and genetic findings in endometriosis and describes the mechanisms whereby genetic and non-genetic factors potentially contribute to the neoplastic progression of endometriosis. Methods: Literature review of the English language literature based on searching in the MEDLINE (PubMed) database and additional collection of reports by systematically reviewing all references from retrieved papers. Results: Atypical endometriosis seems to represent a transition from benign endometriosis to carcinoma. Endometriosis is characterized by genetic instability: like neoplasms endometriosis seems to be monoclonal in origin, several studies have documented loss of heterozygosity (LOH) in endometriosis, data suggest that mutation of the tumor suppressor gene PTEN play a part in the malignant transformation of endometriosis, some studies have revealed TP53 mutations in endometriotic lesions, and mutation of ARID1A seems to be an important early event in the malignant transformation of endometriosis to endometrioid and clear cell carcinomas. Heme and iron induced oxidative stress, inflammation, and hyperestrogenism are possible links between endometriosis and cancer. Conclusions: The histological and genetic alterations in endometriosis seem to explain why endometriosis can be a precursor of some ovarian cancers, especially clear cell and endometrioid carcinomas. However, the exact molecular mechanisms that may lead to this malignant transformation of endometriosis are not completely understood. More and larger studies are needed to clarify how exactly endometriotic tissue undergoes malignant transformation.
MeSH term(s)	Disease Progression ; Endometriosis/genetics ; Endometriosis/metabolism ; Endometriosis/pathology ; Female ; Humans ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Precancerous Conditions/genetics ; Precancerous Conditions/metabolism ; Precancerous Conditions/pathology
Language	English
Publishing date	2012-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2011.10.001
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Article ; Online: The association between endometriosis and gynecological cancers and breast cancer: a review of epidemiological data.

Munksgaard, Peter Svenssen / Blaakaer, Jan

Gynecologic oncology

2011 Volume 123, Issue 1, Page(s) 157–163

Abstract: Objective: This article critically reviews the literature on the association between endometriosis and gynecological cancers and breast cancer, based on epidemiologic data.: Methods: Literature review of the English language literature based on ... ...

Abstract	Objective: This article critically reviews the literature on the association between endometriosis and gynecological cancers and breast cancer, based on epidemiologic data. Methods: Literature review of the English language literature based on searching in the MEDLINE (PubMed) database and additional collection of reports by systematically reviewing all references from retrieved papers. Results: Data from large cohort and case-control studies indicate that endometriosis patients only have an increased risk of ovarian cancer among the gynecological malignancies and breast cancer, although most of the observed associations are modest. Data on the association between endometriosis and breast cancer are inconsistent. Endometriosis patients have a reduced risk of cervical cancer, and there is no association between endometriosis and endometrial cancer. Endometriosis-associated ovarian cancer seems to be a distinct clinical entity; patients are younger, diagnosed in earlier stages, have lower grade lesions and a better survival. Further, endometriosis-associated ovarian cancers are predominantly clear cell and endometrioid histologic subtypes. Conclusions: Endometriosis seems to be a precursor of epithelial ovarian cancer, especially clear cell and endometrioid adenocarcinomas. However, current evidence is insufficient to draw any definitive conclusions whether this association represents causality or the sharing of similar risk factors and/or antecedent mechanisms.
MeSH term(s)	Breast Neoplasms/epidemiology ; Case-Control Studies ; Cohort Studies ; Endometriosis/epidemiology ; Female ; Genital Neoplasms, Female/embryology ; Humans
Language	English
Publishing date	2011-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2011.06.017
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Article: Mazabraud's syndrome: case report and literature review.

Munksgaard, Peter Svenssen / Salkus, Giedrius / Iyer, Victor V / Fisker, Rune Vincents

Acta radiologica short reports

2013 Volume 2, Issue 4, Page(s) 2047981613492532

Abstract: ... on 18F-FDG PET/CT with histopathological confirmation of the myxoma. Our case demonstrates a slightly ...

Abstract	Mazabraud's syndrome is a rare disorder characterized by the association of single or multiple intramuscular myxomas with fibrous dysplasia. Here, we present the first case of Mazabraud's syndrome visualized on 18F-FDG PET/CT with histopathological confirmation of the myxoma. Our case demonstrates a slightly increased FDG uptake (SUVmax 2.1) within the myxomas and a moderately to highly increased tracer uptake (SUVmax 7.0) within the fibrous dysplastic lesions. The typical histological appearance of the intramuscular myxoma confirmed the radiological diagnosis. Further, we discuss the imaging findings and the histopathological features of this rare case with a review of the related literature.
Language	English
Publishing date	2013-05-31
Publishing country	England
Document type	Case Reports
ZDB-ID	2649745-1
ISSN	2047-9816
ISSN	2047-9816
DOI	10.1177/2047981613492532
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Article ; Online: Preexisting Cardiovascular Risk and Subsequent Heart Failure Among Non-Hodgkin Lymphoma Survivors.

Salz, Talya / Zabor, Emily C / de Nully Brown, Peter / Dalton, Susanne Oksberg / Raghunathan, Nirupa J / Matasar, Matthew J / Steingart, Richard / Vickers, Andrew J / Svenssen Munksgaard, Peter / Oeffinger, Kevin C / Johansen, Christoffer

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2017 Volume 35, Issue 34, Page(s) 3837–3843

Abstract: Purpose The use of anthracycline chemotherapy is associated with heart failure (HF) among survivors of non-Hodgkin lymphoma (NHL). We aimed to understand the contribution of preexisting cardiovascular risk factors to HF risk among NHL survivors. Methods ... ...

Abstract	Purpose The use of anthracycline chemotherapy is associated with heart failure (HF) among survivors of non-Hodgkin lymphoma (NHL). We aimed to understand the contribution of preexisting cardiovascular risk factors to HF risk among NHL survivors. Methods Using Danish registries, we identified adults diagnosed with aggressive NHL from 2000 to 2010 and sex- and age-matched general-population controls. We assessed HF from 9 months after diagnosis through 2012. We used Cox regression analysis to assess differences in risk for HF between survivors and general population controls. Among survivors only, preexisting cardiovascular factors (hypertension, dyslipidemia, and diabetes) and preexisting cardiovascular disease were ascertained. We used multivariable Cox regression to model the association of preexisting cardiovascular conditions on subsequent HF. Results Among 2,508 survivors of NHL and 7,399 controls, there was a 42% increased risk of HF among survivors compared with general population controls (hazard ratio [HR], 1.42; 95% CI, 1.07 to 1.88). Among survivors (median age at diagnosis, 62 years; 56% male), 115 were diagnosed with HF during follow-up (median years of follow-up, 2.5). Before NHL diagnosis, 39% had ≥ 1 cardiovascular risk factor; 92% of survivors were treated with anthracycline-containing regimens. In multivariable analysis, intrinsic heart disease diagnosed before lymphoma was associated with increased risk of HF (HR, 2.71; 95% CI, 1.15 to 6.36), whereas preexisting vascular disease had no association with HF ( P > .05). Survivors with cardiovascular risk factors had an increased risk of HF compared with those with none (for 1 v 0 cardiovascular risk factors: HR, 1.63; 95% CI, 1.07 to 2.47; for ≥ 2 v 0 cardiovascular risk factors: HR, 2.86; 95% CI, 1.56 to 5.23; joint P < .01). Conclusion In a large, population-based cohort of NHL survivors, preexisting cardiovascular conditions were associated with increased risk of HF. Preventive approaches should take baseline cardiovascular health into account.
MeSH term(s)	Adult ; Aged ; Anthracyclines/administration & dosage ; Anthracyclines/adverse effects ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/mortality ; Case-Control Studies ; Denmark ; Female ; Heart Failure/epidemiology ; Heart Failure/etiology ; Heart Failure/physiopathology ; Humans ; Lymphoma, Non-Hodgkin/drug therapy ; Lymphoma, Non-Hodgkin/mortality ; Lymphoma, Non-Hodgkin/pathology ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Predictive Value of Tests ; Preexisting Condition Coverage ; Proportional Hazards Models ; Registries ; Retrospective Studies ; Risk Factors ; Survivors
Chemical Substances	Anthracyclines
Language	English
Publishing date	2017-09-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2017.72.4211
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Article ; Online: Anthropometrics and prognosis in diffuse large B-cell lymphoma: a multicentre study of 653 patients.

Bendtsen, Mette Dahl / Munksgaard, Peter Svenssen / Severinsen, Marianne Tang / Bekric, Eric / Brieghel, Christian / Nielsen, Kristina Buchardi / Brown, Peter de Nully / Dybkaer, Karen / Johnsen, Hans Erik / Bøgsted, Martin / El-Galaly, Tarec Christoffer

European journal of haematology

2017 Volume 98, Issue 4, Page(s) 355–362

Abstract: Objective: The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients.: Patients and methods: A total ... ...

Abstract	Objective: The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients. Patients and methods: A total of 653 R-CHOP(-like)-treated DLBCL patients were included in this retrospective cohort study. Patients, baseline clinicopathologic characteristics and treatment information were retrieved from the Danish Lymphoma Registry. Anthropometric measures were obtained from chemotherapy prescription charts. Results: Underweight (BMI <18.5 kg/m Conclusions: Our study demonstrates that underweight DLBCL patients have worse outcomes following R-CHOP as compared to normal as well as overweight patients.
MeSH term(s)	Aged ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Body Mass Index ; Body Surface Area ; Cyclophosphamide/administration & dosage ; Denmark ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/mortality ; Lymphoma, Large B-Cell, Diffuse/pathology ; Male ; Middle Aged ; Overweight ; Prednisone/administration & dosage ; Registries ; Retrospective Studies ; Survival Rate ; Vincristine/administration & dosage
Chemical Substances	Antibodies, Monoclonal, Murine-Derived ; R-CHOP protocol ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2017-04
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Multicenter Study
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.12835
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Article ; Online: The Danish National Lymphoma Registry: Coverage and Data Quality.

Arboe, Bente / El-Galaly, Tarec Christoffer / Clausen, Michael Roost / Munksgaard, Peter Svenssen / Stoltenberg, Danny / Nygaard, Mette Kathrine / Klausen, Tobias Wirenfeldt / Christensen, Jacob Haaber / Gørløv, Jette Sønderskov / Brown, Peter de Nully

PloS one

2016 Volume 11, Issue 6, Page(s) e0157999

Abstract: Background: The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically ...

Abstract	Background: The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. Aim: To test the coverage and data quality of the LYFO. Methods: The coverage was tested by merging data of the LYFO with the Danish Cancer Register and the Danish National Patient Register, respectively. The validity of the LYFO was assessed by crosschecking with information from medical records in subgroups of patients. A random sample of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive values (PPVs) and completeness of selected variables were calculated for each subgroup and for the entire cohort of patients. Results: The comparison of data from the LYFO with the Danish Cancer Register and the Danish National Patient Register revealed a high coverage. In addition, the data quality was good with high PPVs (87% to 100%), and high completeness (92% to 100%). Conclusion: The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research.
MeSH term(s)	Data Accuracy ; Denmark/epidemiology ; Female ; Humans ; Lymphoma/epidemiology ; Male ; Population Surveillance ; Registries/standards ; Registries/statistics & numerical data
Language	English
Publishing date	2016-06-23
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0157999
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Article ; Online: The Danish National Lymphoma Registry

Bente Arboe / Tarec Christoffer El-Galaly / Michael Roost Clausen / Peter Svenssen Munksgaard / Danny Stoltenberg / Mette Kathrine Nygaard / Tobias Wirenfeldt Klausen / Jacob Haaber Christensen / Jette Sønderskov Gørløv / Peter de Nully Brown

PLoS ONE, Vol 11, Iss 6, p e

Coverage and Data Quality.

2016 Volume 0157999

Abstract: BACKGROUND:The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically ... ...

Abstract	BACKGROUND:The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. AIM:To test the coverage and data quality of the LYFO. METHODS:The coverage was tested by merging data of the LYFO with the Danish Cancer Register and the Danish National Patient Register, respectively. The validity of the LYFO was assessed by crosschecking with information from medical records in subgroups of patients. A random sample of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive values (PPVs) and completeness of selected variables were calculated for each subgroup and for the entire cohort of patients. RESULTS:The comparison of data from the LYFO with the Danish Cancer Register and the Danish National Patient Register revealed a high coverage. In addition, the data quality was good with high PPVs (87% to 100%), and high completeness (92% to 100%). CONCLUSION:The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Leukotoxin from Aggregatibacter actinomycetemcomitans causes shrinkage and P2X receptor-dependent lysis of human erythrocytes.

Munksgaard, Peter Svenssen / Vorup-Jensen, Thomas / Reinholdt, Jesper / Söderström, Carl Martin / Poulsen, Knud / Leipziger, Jens / Praetorius, Helle A / Skals, Marianne

Cellular microbiology

2012 Volume 14, Issue 12, Page(s) 1904–1920

Abstract: Leukotoxin (LtxA) is a virulence factor secreted by the bacterium Aggregatibacter actinomycetemcomitans, which can cause localized aggressive periodontitis and endocarditis. LtxA belongs to the repeat-in-toxin (RTX) family of exotoxins of which other ... ...

Abstract	Leukotoxin (LtxA) is a virulence factor secreted by the bacterium Aggregatibacter actinomycetemcomitans, which can cause localized aggressive periodontitis and endocarditis. LtxA belongs to the repeat-in-toxin (RTX) family of exotoxins of which other members inflict lysis by formation of membrane pores. Recently, we documented that the haemolytic process induced by another RTX toxin [α-haemolysin (HlyA) from Escherichia coli] requires P2X receptor activation and consists of sequential cell shrinkage and swelling. In contrast, the cellular and molecular mechanisms of LtxA-mediated haemolysis are not fully understood. Here, we investigate the effect of LtxA on erythrocyte volume and whether P2 receptors also play a part in LtxA-mediated haemolysis. We observed that LtxA initially decreases the cell size, followed by a gradual rise in volume until the cell finally lyses. Moreover, LtxA triggers phosphatidylserine (PS) exposure in the erythrocyte membrane and both the shrinkage and the PS-exposure is preceded by increments in the intracellular Ca(2+) concentration ([Ca(2+)](i)). Interestingly, LtxA-mediated haemolysis is significantly potentiated by ATP release and P2X receptor activation in human erythrocytes. Furthermore, the LtxA-induced [Ca(2+)](i) increase and following volume changes partially depend on P2 receptor activation. Theseobservations imply that intervention against local P2-mediated auto- and paracrine signalling may prevent LtxA-mediated cell damage.
MeSH term(s)	Calcium/analysis ; Cell Size ; Cytoplasm/chemistry ; Erythrocytes/cytology ; Erythrocytes/drug effects ; Escherichia coli ; Exotoxins/toxicity ; Hemolysis ; Humans ; Models, Biological ; Pasteurellaceae/pathogenicity ; Receptors, Purinergic P2X/metabolism
Chemical Substances	Exotoxins ; Receptors, Purinergic P2X ; leukotoxin ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2012-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1468320-9
ISSN	1462-5822 ; 1462-5814
ISSN (online)	1462-5822
ISSN	1462-5814
DOI	10.1111/cmi.12021
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Zs.A 5288: Show issues

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Article ; Online: R-CHOP(-like) treatment of diffuse large B-cell lymphoma significantly reduces CT-assessed vertebral bone density: a single center study of 111 patients.

Svendsen, Pernille / Shekhrajka, Nitesh / Nielsen, Kasper Lindblad / Vestergaard, Peter / Poulsen, Mette Østergaard / Vistisen, Anders Krog / Munksgaard, Peter Svenssen / Severinsen, Marianne Tang / Jensen, Paw / Johnsen, Hans Erik / Jakobsen, Lasse Hjort / Bøgsted, Martin / Frøkjær, Jens Brøndum / El-Galaly, Tarec Christoffer

Leukemia & lymphoma

2016 Volume 58, Issue 5, Page(s) 1105–1113

Abstract: Treatment of diffuse large B-cell lymphoma (DLBCL) with R-CHOP(-like) regimens include large cumulative doses of prednisolone. In this retrospective study, we evaluated changes in vertebral bone density (VD) in DLBCL patients by measuring CT-ascertained ... ...

Abstract	Treatment of diffuse large B-cell lymphoma (DLBCL) with R-CHOP(-like) regimens include large cumulative doses of prednisolone. In this retrospective study, we evaluated changes in vertebral bone density (VD) in DLBCL patients by measuring CT-ascertained Hounsfield units (HU) at the L3 level. In total, 111 patients diagnosed from 2007 to 2012 and response assessed following first line treatment were included. Post-treatment VD was significantly reduced to 86% of pretreatment VD on average (p < .001). Neither female sex nor high age (>70 years) were significantly associated with greater post-treatment VD reduction. Two years after completing R-CHOP treatment, VD remained significantly lower than baseline VD (p < .001). Vertebral compression fractures visualized by CT were found in 16/111 patients (14%) during follow-up. In conclusion, bone mineral density is significantly reduced following R-CHOP(-like) treatment and vertebral compression fractures are common. Glucocorticoid-induced osteoporosis may therefore have impact on survivorship for the large fraction of DLBCL patients with durable remissions.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived/adverse effects ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers ; Bone Density/drug effects ; Combined Modality Therapy ; Cyclophosphamide/adverse effects ; Cyclophosphamide/therapeutic use ; Doxorubicin/adverse effects ; Doxorubicin/therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/mortality ; Male ; Middle Aged ; Odds Ratio ; Positron Emission Tomography Computed Tomography ; Prednisone/adverse effects ; Prednisone/therapeutic use ; Prognosis ; Spine/diagnostic imaging ; Spine/drug effects ; Spine/pathology ; Tomography, X-Ray Computed ; Treatment Outcome ; Vincristine/adverse effects ; Vincristine/therapeutic use ; Young Adult
Chemical Substances	Antibodies, Monoclonal, Murine-Derived ; Biomarkers ; R-CHOP protocol ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2016-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2016.1233543
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Article ; Online: Sialic acid residues are essential for cell lysis mediated by leukotoxin from Aggregatibacter actinomycetemcomitans.

Munksgaard, Peter Svenssen / Skals, Marianne / Reinholdt, Jesper / Poulsen, Knud / Jensen, Maria Risager / Yang, Chuanxu / Leipziger, Jens / Vorup-Jensen, Thomas / Praetorius, Helle A

Infection and immunity

2014 Volume 82, Issue 6, Page(s) 2219–2228

Abstract: Leukotoxin (LtxA) from Aggregatibacter actinomycetemcomitans is known to target and lyse β2-integrin-expressing cells such as polymorphonuclear leukocytes and macrophages. LtxA is an important virulence factor that facilitates chronic inflammation and is ...

Abstract	Leukotoxin (LtxA) from Aggregatibacter actinomycetemcomitans is known to target and lyse β2-integrin-expressing cells such as polymorphonuclear leukocytes and macrophages. LtxA is an important virulence factor that facilitates chronic inflammation and is strongly associated with a fast-progressing form of periodontitis caused by the JP2 clone of the bacterium. Here, we show that sialic acid residues are important for LtxA-induced cell lysis, regardless of whether the cell express β2-integrin or not. Clearly, removal of sialic acid groups significantly reduces a β2-integrin-specific LtxA-induced lysis. Moreover, sialic acid presented on alternative proteins, such as, for instance, on erythrocytes that do not express β2-integrin, also makes the cells more sensitive to LtxA. The data also illustrate the importance of the negative charge in order for the sialic acid to associate LtxA with the membrane. Removal of sialic acid is in itself sufficient to significantly reduce the negative charge on the erythrocytes. Moreover, we found that on human erythrocytes there is a positive association between the sensitivity to LtxA and the amount of negative charge caused by sialic acid. Interestingly, these features are not shared by all RTX toxins, since α-hemolysin from Escherichia coli induced cell lysis of both β2-integrin-expressing and nonexpressing cells and this lysis is independent of the presence of sialic acid residues. In conclusion, LtxA not only is cytotoxic to β2-integrin-expressing cells but can potentially initiate cell lysis in all cells that present a sufficient density of sialic acid groups on their plasma membrane.
MeSH term(s)	Aggregatibacter actinomycetemcomitans/physiology ; Analysis of Variance ; Animals ; CD18 Antigens/physiology ; Cell Death/drug effects ; Cell Death/physiology ; Cell Line ; Erythrocytes/drug effects ; Erythrocytes/metabolism ; Exotoxins/physiology ; Exotoxins/toxicity ; Humans ; Mice ; N-Acetylneuraminic Acid/chemistry ; N-Acetylneuraminic Acid/physiology ; Rabbits ; Sheep
Chemical Substances	CD18 Antigens ; Exotoxins ; leukotoxin ; N-Acetylneuraminic Acid (GZP2782OP0)
Language	English
Publishing date	2014-03-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.01647-14
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In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito