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Rankin, Gregory
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Publications (10 of 21) Show all publications
Lepzien, R., Rankin, G., Pourazar, J., Muala, A., Eklund, A., Grunewald, J., . . . Smed-Sorensen, A. (2019). Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients. Journal of Leukocyte Biology, 105(4), 797-807
Open this publication in new window or tab >>Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients
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2019 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 105, no 4, p. 797-807Article in journal (Refereed) Published
Abstract [en]

Sarcoidosis is a T-cell driven inflammatory disease characterized by granuloma formation. Mononuclear phagocytes (MNPs)-macrophages, monocytes, and dendritic cells (DCs)-are likely critical in sarcoidosis as they initiate and maintain T cell activation and contribute to granuloma formation by cytokine production. Granulomas manifest primarily in lungs and lung-draining lymph nodes (LLNs) but these compartments are less studied compared to blood and bronchoalveolar lavage (BAL). Sarcoidosis can present with an acute onset (usually Lofgren's syndrome (LS)) or a gradual onset (non-LS). LS patients typically recover within 2 years while 60% of non-LS patients maintain granulomas for up to 5 years. Here, four LS and seven non-LS patients underwent bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). From each patient, blood, BAL, endobronchial biopsies (EBBs), and LLN samples obtained by EBUS-TBNA were collected and MNPs characterized using multicolor flow cytometry. Six MNP subsets were identified at varying frequencies in the anatomical compartments investigated. Importantly, monocytes and DCs were most mature with migratory potential in BAL and EBBs but not in the LLNs suggesting heterogeneity in MNPs in the compartments typically affected in sarcoidosis. Additionally, in LS patients, frequencies of DC subsets were lower or lacking in LLNs and EBBs, respectively, compared to non-LS patients that may be related to the disease outcome. Our work provides a foundation for future investigations of MNPs in sarcoidosis to identify immune profiles of patients at risk of developing severe disease with the aim to provide early treatment to slow down disease progression.

Place, publisher, year, edition, pages
Society for Leukocyte Biology, 2019
Keywords
dendritic cell, monocyte, sarcoidosis, lymph node, Lofgren's syndrome
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-158084 (URN)10.1002/JLB.5A0718-280RR (DOI)000462155000015 ()30742337 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research Council
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-04-15Bibliographically approved
Rankin, G., Byström, J. W., Gustafsson, R., Hansson, M., Thunberg, T., Ahlm, C. & Connolly, A.-M. F. (2019). MMP9 Associates with Endothelial Glycocalyx Degradation During Haemorrhagic Fever with Renal Syndrome. Paper presented at 3rd Joint Meeting of the European-Society-for-Microcirculation (ESM) and the European-Vascular-Biology-Organization (EVBO), Maastricht, Netherlands, April, 2019.. Journal of Vascular Research, 56, 35-35
Open this publication in new window or tab >>MMP9 Associates with Endothelial Glycocalyx Degradation During Haemorrhagic Fever with Renal Syndrome
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2019 (English)In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 56, p. 35-35Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Introduction: Haemorrhagic fever with renal syndrome (HFRS) is characterized by fever, hypotension, vascular leakage, thrombocytopenia and renal failure. HFRS in Sweden is caused by the Puumala hantavirus and is spread by viral-infested droppings from bank voles. The health care system has little to offer these patients since there is no antiviral treatment and as of yet there is no vaccine prophylaxis available. We previously showed that a marker of endothelial glycocalyx degradation (Syndecan-1) was associated with disease severity and disseminated intravascular coagulation during HFRS (Connolly-Andersen et al., 2014, Open Forum Infect Dis.).

Methods: We analysed the levels of other endothelial glycocalyx degradation markers (heparan sulfate, soluble thrombomodulin, albumin), a potential “sheddase”: Matrix Metalloproinase 9 (MMP9) and neutrophil activation/tissue damage (neutrophil gelatinase-associated lipocalin, NGAL) in patient plasma from 44 HFRS patients collected consecutively following disease onset. We used the generalized estimating equation to analyse the association between endothelial glycocalyx degradation, MMP9 levels, neutrophil activation/tissue damage and HFRS disease outcome (need for oxygen, transfusion with blood components, need for intensive care unit (ICU) treatment and renal damage).

Results: 44 HFRS patients were included in this study (29 females (66%)); need for oxygen: 11 (25%); transfusion with blood components: 3 (7%) and stay at ICU: 2 (5%)). The levels of MMP9 were significantly associated with all markers of endothelial glycocalyx degradation. Neutrophil activation/tissue damage (NGAL) was also significantly associated with MMP9 and endothelial glycocalyx degradation markers (apart from albumin (p = 0.053). In addition degradation of endothelial glycocalyx associated with HFRS disease outcome.

Conclusion: Degradation of the endothelial glycocalyx could be a potential mechanism of HFRS pathogenesis, and potentially MMP9 could contribute to degradation of the endothelial glycocalyx

Place, publisher, year, edition, pages
S. Karger, 2019
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-158767 (URN)10.1159/000499516 (DOI)000463529300074 ()
Conference
3rd Joint Meeting of the European-Society-for-Microcirculation (ESM) and the European-Vascular-Biology-Organization (EVBO), Maastricht, Netherlands, April, 2019.
Note

Supplement 1, meeting abstract 73.

Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-05-08
Rankin, G. D., Wingfors, H., Uski, O., Hedman, L., Ekstrand-Hammarström, B., Bosson, J. & Lundbäck, M. (2019). The toxic potential of a fourth-generation E-cigarette on human lung cell lines and tissue explants. Journal of Applied Toxicology, 39(8), 1143-1154
Open this publication in new window or tab >>The toxic potential of a fourth-generation E-cigarette on human lung cell lines and tissue explants
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2019 (English)In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 39, no 8, p. 1143-1154Article in journal (Refereed) Published
Abstract [en]

The use of electronic cigarettes (E‐cigs) is rapidly increasing. The latest generation of E‐cigs is highly customizable, allowing for high heating coil temperatures. The aim of this study was to assess the toxic potential of a fourth‐generation E‐cig. Aerosols generated from E‐liquid with (24 mg/mL) and without nicotine, using a fourth‐generation E‐cig, were chemically analysed and compared with cigarette smoke (K3R4F). Human lung epithelial cell lines and distal lung tissue explants were exposed to E‐cig vapour extract (EVE) and cigarette smoke extract for 24 hours and assessed for viability, inflammation, oxidative stress and genotoxicity. E‐cig aerosols contained measurable levels of volatile organic compounds, aldehydes and polycyclic aromatic hydrocarbons, in general, to a much lesser extent than cigarette smoke. Higher levels of certain carbonyls, e.g. formaldehyde, were detected in the E‐cig aerosols. EVEs decreased cell viability of BEAS‐2B cells, whereas little effect was seen in A549 cells and distal lung tissue. The nicotine‐containing EVE caused a greater decrease in cell viability and significant increase in DNA damage than the nicotine‐free EVE. Increased cytotoxicity, reactive oxygen species production and genotoxicity were seen with cells and tissue exposed to cigarette smoke extract compared with EVEs. Although E‐cig aerosols were less toxic than cigarette smoke, it was not benign. Moreover, the EVE containing nicotine was more toxic than the nicotine‐free EVE. More research is needed on the short‐ and long‐term health effects of vaping and the usage of newly emerging E‐cig devices to evaluate better the potential negative effects of E‐cigs on human health.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
A549, BEAS-2B, DNA damage, aerosol characterization, cell cycle, electronic cigarette extract, human distal lung tissue, inflammatory cytokines, viability
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-158814 (URN)10.1002/jat.3799 (DOI)000475406700006 ()30957912 (PubMedID)2-s2.0-85063979647 (Scopus ID)
Available from: 2019-05-09 Created: 2019-05-09 Last updated: 2019-08-12Bibliographically approved
Rankin, G., Kabele, M., Sandström, T., Brown, R., Macefield, V. G. & Bosson, J. A. (2018). Diesel exhaust exposure increases muscle sympathetic nerve activity Study: a human exposure. Paper presented at International Conference of the American-Thoracic-Society, MAY 18-23, 2018, San Diego, CA. American Journal of Respiratory and Critical Care Medicine, 197
Open this publication in new window or tab >>Diesel exhaust exposure increases muscle sympathetic nerve activity Study: a human exposure
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2018 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Thoraric Society, 2018
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-154091 (URN)000449980303080 ()
Conference
International Conference of the American-Thoracic-Society, MAY 18-23, 2018, San Diego, CA
Funder
Västerbotten County CouncilForte, Swedish Research Council for Health, Working Life and WelfareSwedish Research Council Formas
Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2018-12-12Bibliographically approved
Uski, O., Rankin, G., Lindgren, R., Lopez, N., Blomberg, A., Muala, A., . . . Sandström, T. (2018). In vitro toxicity of particulate matter derived from biomass cook stoves used in developing countries. Paper presented at International Conference of the American-Thoracic-Society, MAY 18-23, 2018, San Diego, CA. American Journal of Respiratory and Critical Care Medicine, 197
Open this publication in new window or tab >>In vitro toxicity of particulate matter derived from biomass cook stoves used in developing countries
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2018 (English)In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Thoraric Society, 2018
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-154090 (URN)000449978902089 ()
Conference
International Conference of the American-Thoracic-Society, MAY 18-23, 2018, San Diego, CA
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Heart Lung Foundation
Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2018-12-12Bibliographically approved
Lepzien, R., Rankin, G., Pourazar, J., Muala, A., Eklund, A., Grunewald, J., . . . Sörensen, A. S. (2018). Mononuclear phagocytes in lungs, lymph nodes and blood of sarcoidosis patients. Paper presented at 28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE. European Respiratory Journal, 52
Open this publication in new window or tab >>Mononuclear phagocytes in lungs, lymph nodes and blood of sarcoidosis patients
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2018 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Introduction: Sarcoidosis is characterized by granuloma formation primarily in the lung and lung-draining lymph nodes (LN). The disease can present with an acute onset (usually Löfgren’s syndrome (LS)) or a gradual onset (non-LS). Mononuclear phagocytes (MNPs) - macrophages, monocytes and dendritic cells (DC) - are likely critical in sarcoidosis as they initiate and maintain T cell activation and contribute to granuloma formation by production of cytokines. MNPs in lung tissue and LN are poorly studied in both, non-LS and LS sarcoidosis patients.

Aim: To characterise the distribution and phenotype of MNPs in BAL, endobronchial biopsies (EBB), LN sampled by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and blood from the same non-LS or LS sarcoidosis patients.

Results: We identified MNPs from all four anatomical compartments in non-LS (n=7) and LS (n=4) sarcoidosis patients. Blood, BAL and LN contained all MNP subsets while EBB only harboured one of three monocyte subsets. Frequencies, maturation and migratory status were different between the compartments as well as between non-LS and LS patients. Our results suggest heterogeneity in distribution and function of MNPs within organs typically affected in sarcoidosis and their potential involvement in the disease course.

Conclusions: We show that cells from BAL fluid do not necessarily reflect cells from EBB, a tissue primarily affected by granuloma formation. Our work provides a foundation for future investigations of MNPs in non-LS and LS sarcoidosis patients, allowing improved stratification to identify patients at risk of developing severe disease and provide early treatment to slow down disease progression.

Place, publisher, year, edition, pages
European Respiratory Society, 2018
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-156002 (URN)10.1183/13993003.congress-2018.PA5205 (DOI)000455567107030 ()
Conference
28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE
Note

Supplement: 62

Meeting Abstract: PA5205

Available from: 2019-02-01 Created: 2019-02-01 Last updated: 2019-02-01Bibliographically approved
Scholz, S., Baharom, F., Rankin, G., Maleki, K. T., Gupta, S., Vangeti, S., . . . Smed-Sörensen, A. (2017). Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways. PLoS Pathogens, 13(6), Article ID e1006462.
Open this publication in new window or tab >>Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways
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2017 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 13, no 6, article id e1006462Article in journal (Refereed) Published
Abstract [en]

Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS). Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.

Place, publisher, year, edition, pages
Public library science, 2017
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-137809 (URN)10.1371/journal.ppat.1006462 (DOI)000404511700047 ()28640917 (PubMedID)
Available from: 2017-07-26 Created: 2017-07-26 Last updated: 2018-06-09Bibliographically approved
Baharom, F., Rankin, G., Scholz, S., Pourazar, J., Ahlm, C., Blomberg, A. & Smed-Sörensen, A. (2017). Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry. Jove-journal pf visualized experiments (119), Article ID e55222.
Open this publication in new window or tab >>Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry
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2017 (English)In: Jove-journal pf visualized experiments, ISSN 1940-087X, no 119, article id e55222Article in journal (Refereed) Published
Abstract [en]

The lungs are constantly exposed to the external environment, which in addition to harmless particles, also contains pathogens, allergens, and toxins. In order to maintain tolerance or to induce an immune response, the immune system must appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in maintaining a delicate balance to initiate immunity when required without causing collateral damage to the lungs due to an exaggerated inflammatory response. While there is a detailed understanding of the phenotype and function of immune cells such as DCs in human blood, the knowledge of these cells in less accessible tissues, such as the lungs, is much more limited, since studies of human lung tissue samples, especially from healthy individuals, are scarce. This work presents a strategy to generate detailed spatial and phenotypic characterization of lung tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling of endobronchial biopsies. Several small biopsies can be collected from each individual and can be subsequently embedded for ultrafine sectioning or enzymatically digested for advanced flow cytometric analysis. The outlined protocols have been optimized to yield maximum information from small tissue samples that, under steady-state conditions, contain only a low frequency of DCs. While the present work focuses on DCs, the methods described can directly be expanded to include other (immune) cells of interest found in mucosal lung tissue. Furthermore, the protocols are also directly applicable to samples obtained from patients suffering from pulmonary diseases where bronchoscopy is part of establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD), sarcoidosis, or lung cancer.

Place, publisher, year, edition, pages
Cambridge: MyJoVE Corp., 2017
Keywords
Immunology, Issue 119, bronchoscopy, monocyte, dendritic cell, tissue digestion, munohistochemistry, flow cytometry
National Category
Respiratory Medicine and Allergy Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-133678 (URN)10.3791/55222 (DOI)000397847200073 ()
Available from: 2017-04-20 Created: 2017-04-20 Last updated: 2018-06-09Bibliographically approved
Baharom, F., Rankin, G., Blomberg, A. & Smed-Sorensen, A. (2017). Human Lung Mononuclear Phagocytes in Health and Disease. Frontiers in Immunology, 8, Article ID 499.
Open this publication in new window or tab >>Human Lung Mononuclear Phagocytes in Health and Disease
2017 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 499Article, review/survey (Refereed) Published
Abstract [en]

The lungs are vulnerable to attack by respiratory insults such as toxins, allergens, and pathogens, given their continuous exposure to the air we breathe. Our immune system has evolved to provide protection against an array of potential threats without causing collateral damage to the lung tissue. In order to swiftly detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs)-together termed mononuclear phagocytes (MNPs)-line the respiratory tract with the key task of surveying the lung microenvironment in order to discriminate between harmless and harmful antigens and initiate immune responses when necessary. Each cell type excels at specific tasks: monocytes produce large amounts of cytokines, macrophages are highly phagocytic, whereas DCs excel at activating naive T cells. Extensive studies in murine models have established a division of labor between the different populations of MNPs at steady state and during infection or inflammation. However, a translation of important findings in mice is only beginning to be explored in humans, given the challenge of working with rare cells in inaccessible human tissues. Important progress has been made in recent years on the phenotype and function of human lung MNPs. In addition to a substantial population of alveolar macrophages, three subsets of DCs have been identified in the human airways at steady state. More recently, monocyte-derived cells have also been described in healthy human lungs. Depending on the source of samples, such as lung tissue resections or bronchoalveolar lavage, the specific subsets of MNPs recovered may differ. This review provides an update on existing studies investigating human respiratory MNP populations during health and disease. Often, inflammatory MNPs are found to accumulate in the lungs of patients with pulmonary conditions. In respiratory infections or inflammatory diseases, this may contribute to disease severity, but in cancer patients this may improve clinical outcomes. By expanding on this knowledge, specific lung MNPs may be targeted or modulated in order to attain favorable responses that can improve preventive or treatment strategies against respiratory infections, lung cancer, or lung inflammatory diseases.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2017
Keywords
respiratory, pulmonary, monocytes, dendritic cells, macrophages, bronchoalveolar lavage, lung tissue, onchial tissue
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-136191 (URN)10.3389/fimmu.2017.00499 (DOI)000400317900002 ()28507549 (PubMedID)
Available from: 2017-07-07 Created: 2017-07-07 Last updated: 2019-05-21Bibliographically approved
Pourazar, J., Rankin, G. D., Muala, A., Unosson, J., Sehlstedt, M., Behndig, A. F., . . . Sandstrom, T. (2016). Bronchoalveolar Eosinophilia In Human Subjects After Exposure To Biomass Smoke From Wood Pellet Combustion. In: : . Paper presented at International Conference of the American-Thoracic-Society (ATS), MAY 13-18, 2016, San Francisco, CA. , 193
Open this publication in new window or tab >>Bronchoalveolar Eosinophilia In Human Subjects After Exposure To Biomass Smoke From Wood Pellet Combustion
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2016 (English)Conference paper, Oral presentation with published abstract (Refereed)
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-131011 (URN)000390749607595 ()
Conference
International Conference of the American-Thoracic-Society (ATS), MAY 13-18, 2016, San Francisco, CA
Available from: 2017-02-09 Created: 2017-02-09 Last updated: 2018-06-09Bibliographically approved
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