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Behndig, Annelie F.
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Publications (10 of 49) Show all publications
Karlsson, A., Cirenajwis, H., Ericson-Lindquist, K., Brunnström, H., Reuterswärd, C., Jönsson, M., . . . Staaf, J. (2019). A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer. Scientific Reports, 9, Article ID 5207.
Open this publication in new window or tab >>A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 5207Article in journal (Refereed) Published
Abstract [en]

Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11-199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-158094 (URN)10.1038/s41598-019-41585-4 (DOI)000462298600094 ()30914778 (PubMedID)
Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-04-12Bibliographically approved
Salomonsson, A., Patthey, A., Reuterswärd, C., Jönsson, M., Botling, J., Brunnström, H., . . . Planck, M. (2018). A Nation-Wide Population-Based Mapping of Targetable Alterations in Smoking-Independent Lung Cancer. Journal of Thoracic Oncology, 13(10), S431-S432
Open this publication in new window or tab >>A Nation-Wide Population-Based Mapping of Targetable Alterations in Smoking-Independent Lung Cancer
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2018 (English)In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 10, p. S431-S432Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Smoking is by far the most important cause of lung cancer. However, lung cancer among never-smokers is common and increasing [1]. A smoking-independent subgroup of lung adenocarcinoma with certain molecular and clinical features exists [2-3]. Therefore, as 1st project within the Swedish Molecular Initiative against Lung cancer (SMIL) we aim to characterize never-smoking lung cancer for etiological, diagnostic and therapeutic purposes.

Method: Through the Swedish National Lung Cancer Registry [1], we identified all individuals who underwent surgery for lung cancer in Sweden 2005-2014 and who were registered as never-smokers (n=540). At each study site (n=6), clinical data were reviewed by a thoracic oncologist/pulmonologist through patients' medical charts and archived tumor tissues were retrieved and reviewed by a thoracic pathologist. For subsequent studies, we extracted DNA and RNA (using the Qiagen AllPrep kit for FFPE tissue) and constructed tissue microarrays. As a first pre-planned analysis, we performed fusion gene mapping using an RNA-based NanoString nCounter Elements assay, as previously described [4].

Result: In the first 212 (out of 540) analyzed samples, we detected 17 fusions involving ALK, 8 involving RET, and 2 involving NRG1. In addition, MET exon 14 skipping was found in 17 samples. In total, these findings involved 21% of analyzed cases. Additional results from further studies on the cohort will be presented.

Conclusion: SMIL is an ongoing nation-wide molecular research collaboration on lung cancer where we currently collect one of the largest never-smoking lung tumor cohorts worldwide. From the first pre-planned analyses, we conclude that, in a population-based cohort of early stage lung cancer from never-smokers, druggable oncogenic fusions are frequent.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
population-based, never-smoker, gene fusion
National Category
Cancer and Oncology Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-155249 (URN)10.1016/j.jtho.2018.08.497 (DOI)000454014501133 ()
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-03-18Bibliographically approved
Eriksson Ström, J., Pourazar, J., Linder, R., Blomberg, A., Lindberg, A., Bucht, A. & Behndig, A. F. (2018). Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking. Respiratory Research, 19, Article ID 244.
Open this publication in new window or tab >>Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking
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2018 (English)In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 19, article id 244Article in journal (Refereed) Published
Abstract [en]

Background: Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.

Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.

Results: In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years. Within the COPD group, NK cells – but not iNKT or NKT-like cells – were significantly elevated also in subjects that had quit smoking. In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells. Rate of lung function decline did not significantly affect any of the results.

Conclusions: In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD. Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.

Trial registration: Clinicaltrials.gov identifier NCT02729220.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Chronic obstructive pulmonary disease, Disease mechanisms, Lung function decline, Smoking habits, Bronchoalveolar lavage
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-154873 (URN)10.1186/s12931-018-0940-7 (DOI)000452747200001 ()30526599 (PubMedID)2-s2.0-85058092775 (Scopus ID)
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-01-04Bibliographically approved
Tydén, J., Larsson, N., Lehtipalo, S., Herwald, H., Hultin, M., Walldén, J., . . . Johansson, J. (2018). Heparin-binding protein in ventilator-induced lung injury.. Intensive Care Medicine Experimental, 6(1), Article ID 33.
Open this publication in new window or tab >>Heparin-binding protein in ventilator-induced lung injury.
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2018 (English)In: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 6, no 1, article id 33Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Although mechanical ventilation is often lifesaving, it can also cause injury to the lungs. The lung injury is caused by not only high pressure and mechanical forces but also by inflammatory processes that are not fully understood. Heparin-binding protein (HBP), released by activated granulocytes, has been indicated as a possible mediator of increased vascular permeability in the lung injury associated with trauma and sepsis. We investigated if HBP levels were increased in the bronchoalveolar lavage fluid (BALF) or plasma in a pig model of ventilator-induced lung injury (VILI). We also investigated if HBP was present in BALF from healthy volunteers and in intubated patients in the intensive care unit (ICU).

METHODS: Anaesthetized pigs were randomized to receive ventilation with either tidal volumes of 8 ml/kg (controls, n = 6) or 20 ml/kg (VILI group, n = 6). Plasma and BALF samples were taken at 0, 1, 2, 4, and 6 h. In humans, HBP levels in BALF were sampled from 16 healthy volunteers and from 10 intubated patients being cared for in the ICU.

RESULTS: Plasma levels of HBP did not differ between pigs in the control and VILI groups. The median HBP levels in BALF were higher in the VILI group after 6 h of ventilation compared to those in the controls (1144 ng/ml (IQR 359-1636 ng/ml) versus 89 ng/ml (IQR 33-191 ng/ml) ng/ml, respectively, p = 0.02). The median HBP level in BALF from healthy volunteers was 0.90 ng/ml (IQR 0.79-1.01 ng/ml) as compared to 1959 ng/ml (IQR 612-3306 ng/ml) from intubated ICU patients (p < 0.001).

CONCLUSIONS: In a model of VILI in pigs, levels of HBP in BALF increased over time compared to controls, while plasma levels did not differ between the two groups. HBP in BALF was high in intubated ICU patients in spite of the seemingly non-harmful ventilation, suggesting that inflammation from other causes might increase HBP levels.

Place, publisher, year, edition, pages
SpringerOpen, 2018
Keywords
HBP, Neutrophils, Pigs, Ventilator-induced lung injury
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:umu:diva-151814 (URN)10.1186/s40635-018-0198-x (DOI)000445485300001 ()30203380 (PubMedID)
Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2019-09-02Bibliographically approved
Gouveia-Figueira, S. C., Karimpour, M., Bosson, J. A., Blomberg, A., Unosson, J., Sehlstedt, M., . . . Nording, M. L. (2018). Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust. Analytica Chimica Acta, 1018, 62-69
Open this publication in new window or tab >>Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust
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2018 (English)In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1018, p. 62-69Article in journal (Refereed) Published
Abstract [en]

Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF(2 alpha), 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Oxylipin, Endocannabinoid, Eicosanoid, Mass spectrometry, Rapeseed methyl ester, Inflammation
National Category
Occupational Health and Environmental Health Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-148622 (URN)10.1016/j.aca.2018.02.032 (DOI)000428798200008 ()29605135 (PubMedID)
Funder
Swedish Research Council, 2010-303AFA Insurance, 130320
Available from: 2018-06-26 Created: 2018-06-26 Last updated: 2018-06-26Bibliographically approved
Linder, R., Rönmark, E., Pourazar, J., Behndig, A. F., Blomberg, A. & Lindberg, A. (2018). Proteolytic biomarkers are related to prognosis in COPD: report from a population-based cohort. Respiratory Research, 19, Article ID 64.
Open this publication in new window or tab >>Proteolytic biomarkers are related to prognosis in COPD: report from a population-based cohort
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2018 (English)In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 19, article id 64Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The imbalance between proteases and anti-proteases is considered to contribute to the development of COPD. Our aim was to evaluate the protease MMP-9, the antiprotease TIMP-1 and the MMP-9/TIMP-1-ratio as biomarkers in relation to prognosis. Prognosis was assessed as lung function decline and mortality. This was done among subjects with COPD in a population-based cohort.

METHODS: In 2005, clinical examinations including spirometry and peripheral blood sampling, were made in a longitudinal population-based cohort. In total, 1542 individuals participated, whereof 594 with COPD. In 2010, 1031 subjects participated in clinical examinations, and 952 subjects underwent spirometry in both 2005 and 2010. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbent assay (ELISA). Mortality data were collected from the Swedish national mortality register from the date of examination in 2005 until 31st December 2010.

RESULTS: The correlation between biomarkers and lung function decline was similar in non-COPD and COPD, but only significant for MMP-9 and MMP-9/TIMP-1-ratio in non-COPD. Mortality was higher in COPD than non-COPD (16% vs. 10%, p = 0.008). MMP-9 concentrations and MMP-9/TIMP-1 ratios in 2005 were higher among those who died during follow up, as well as among those alive but not participating in 2010, when compared to those participating in the 2010-examination. In non-COPD, male sex, age, burden of smoking, heart disease and MMP-9/TIMP-1 ratio were associated with increased risk for death, while increased TIMP-1 was protective. Among those with COPD, age, current smoking, increased MMP-9 and MMP-9/TIMP-1 ratio were associated with an increased risk for death.

CONCLUSIONS: The expected association between these biomarkers and lung function decline in COPD was not confirmed in this population-based study, probably due to a healthy survivor effect. Still, it is suggested that increased proteolytic imbalance may be of greater prognostic importance in COPD than in non-COPD.

Place, publisher, year, edition, pages
London: BioMed Central, 2018
Keywords
Chronic obstructive pulmonary disease (COPD), Matrix metalloproteinases, Mortality, Spirometry, Tissue inhibitor of metalloproteinases
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-146657 (URN)10.1186/s12931-018-0772-5 (DOI)000429829100001 ()29650051 (PubMedID)
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2019-08-08Bibliographically approved
Kumar, A., Bicer, E. M., Pfeffer, P., Monopoli, M. P., Dawson, K. A., Eriksson, J., . . . Mudway, I. (2017). Differences in the coronal proteome acquired by particles depositing in the lungs of asthmatic versus healthy humans. Nanomedicine: Nanotechnology, Biology and Medicine, 13(8), 2517-2521
Open this publication in new window or tab >>Differences in the coronal proteome acquired by particles depositing in the lungs of asthmatic versus healthy humans
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2017 (English)In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 13, no 8, p. 2517-2521Article in journal (Refereed) Published
Abstract [en]

Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLFs). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines. The asthmatic coronal proteome displayed a reduced contribution of surfactant proteins (SP-A and B) and a higher contribution of alpha 1-antitrypsin. Pathway analysis suggested that asthmatic RTLFs may also be deficient in proteins related to metal handling (e.g. lactoferrin). This study demonstrates how the composition of the corona acquired by inhaled nanoparticles is modified in asthma and suggests depressed mucosal immunity even in mild airway disease.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-141976 (URN)10.1016/j.nano.2017.06.008 (DOI)000414301400013 ()28647590 (PubMedID)
Available from: 2017-12-06 Created: 2017-12-06 Last updated: 2018-06-09Bibliographically approved
Lindberg, A., Linder, R., Backman, H., Eriksson Ström, J., Frølich, A., Nilsson, U., . . . Blomberg, A. (2017). From COPD epidemiology to studies of pathophysiological disease mechanisms: challenges with regard to study design and recruitment process. European Clinical Respiratory Journal, 4, Article ID 1415095.
Open this publication in new window or tab >>From COPD epidemiology to studies of pathophysiological disease mechanisms: challenges with regard to study design and recruitment process
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2017 (English)In: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 4, article id 1415095Article in journal (Refereed) Published
Abstract [en]

Background: Chronic obstructive pulmonary disease (COPD) is a largely underdiagnosed disease including several phenotypes. In this report, the design of a study intending to evaluate the pathophysiological mechanism in COPD in relation to the specific phenotypes non-rapid and rapid decline in lung function is described together with the recruitment process of the study population derived from a population based study.

Method: The OLIN COPD study includes a population-based COPD cohort and referents without COPD identified in 2002–04 (n = 1986), and thereafter followed annually since 2005. Lung function decline was estimated from baseline in 2002–2004 to 2010 (first recruitment phase) or to 2012/2013 (second recruitment phase). Individuals who met the predefined criteria for the following four groups were identified; group A) COPD grade 2–3 with rapid decline in FEV1 and group B) COPD grade 2–3 without rapid decline in FEV1 (≥60 and ≤30 ml/year, respectively), group C) ever-smokers, and group D) non-smokers with normal lung function. Groups A–C included ever-smokers with >10 pack years. The intention was to recruit 15 subjects in each of the groups A-D.

Results: From the database groups A–D were identified; group A n = 37, group B n = 29, group C n = 41, and group D n = 55. Fifteen subjects were recruited from groups C and D, while this goal was not reached in the groups A (n = 12) and B (n = 10). The most common reasons for excluding individuals identified as A or B were comorbidities contraindicating bronchoscopy, or inflammatory diseases/immune suppressive medication expected to affect the outcome.

Conclusion: The study is expected to generate important results regarding pathophysiological mechanisms associated with rate of decline in lung function among subjects with COPD and the in-detail described recruitment process, including reasons for non-participation, is a strength when interpreting the results in forthcoming studies.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
Chronic obstructive pulmonary disease, disease mechanisms, lung function decline, smoking habits
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine; Epidemiology
Identifiers
urn:nbn:se:umu:diva-143251 (URN)10.1080/20018525.2017.1415095 (DOI)000418831000001 ()
Projects
OLIN-studierna
Available from: 2017-12-19 Created: 2017-12-19 Last updated: 2018-09-12Bibliographically approved
Gouveia-Figueira, S., Karimpour, M., Bosson, J. A., Blomberg, A., Unosson, J., Pourazar, J., . . . Nording, M. L. (2017). Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure. Analytical and Bioanalytical Chemistry, 409(11), 2967-2980
Open this publication in new window or tab >>Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure
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2017 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, no 11, p. 2967-2980Article in journal (Refereed) Published
Abstract [en]

The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 mu g/m(3)) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, Nacylethanolamines, and related lipid metabolites in the collected BWand BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE2, 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG, 2017
Keywords
BAL, BW, Lipidome, Air pollution, Bronchoscopy, Eicosanoid
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-134210 (URN)10.1007/s00216-017-0243-8 (DOI)000398515900019 ()28235994 (PubMedID)
Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2018-06-09Bibliographically approved
Baharom, F., Thomas, S., Rankin, G., Lepzien, R., Pourazar, J., Behndig, A. F., . . . Smed-Sorensen, A. (2016). Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans. Journal of Immunology, 196(11), 4498-4509
Open this publication in new window or tab >>Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans
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2016 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, no 11, p. 4498-4509Article in journal (Refereed) Published
Abstract [en]

Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-123437 (URN)10.4049/jimmunol.1600071 (DOI)000377676000010 ()27183618 (PubMedID)
Available from: 2016-07-20 Created: 2016-07-04 Last updated: 2018-06-07Bibliographically approved
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