| 1. |
- Berlin, Frida, et al.
(författare)
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Mast Cell Proteases Tryptase and Chymase Induce Migratory and Morphological Alterations in Bronchial Epithelial Cells
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 22:10
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Tidskriftsartikel (refereegranskat)abstract
- Chronic respiratory diseases are often characterized by impaired epithelial function and remodeling. Mast cells (MCs) are known to home into the epithelium in respiratory diseases, but the MC-epithelial interactions remain less understood. Therefore, this study aimed to investigate the effect of MC proteases on bronchial epithelial morphology and function. Bronchial epithelial cells were stimulated with MC tryptase and/or chymase. Morphology and epithelial function were performed using cell tracking analysis and holographic live-cell imaging. Samples were also analyzed for motility-associated gene expression. Immunocytochemistry was performed to compare cytoskeletal arrangement. Stimulated cells showed strong alterations on gene, protein and functional levels in several parameters important for maintaining epithelial function. The most significant increases were found in cell motility, cellular speed and cell elongation compared to non-stimulated cells. Also, cell morphology was significantly altered in chymase treated compared to non-stimulated cells. In the current study, we show that MC proteases can induce cell migration and morphological and proliferative alterations in epithelial cells. Thus, our data imply that MC release of proteases may play a critical role in airway epithelial remodeling and disruption of epithelial function.
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| 2. |
- Mogren, Sofia, et al.
(författare)
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Mast cell tryptase enhances wound healing by promoting migration in human bronchial epithelial cells
- 2021
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Ingår i: Cell Adhesion and Migration. - : Informa UK Limited. - 1933-6918 .- 1933-6926. ; 15:1, s. 202-214
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial damage and increase of intraepithelial mast cells (MC) are characteristics of asthma. The role of MC mediator tryptase and the protease-activated receptor-2 (PAR2) on epithelial wound healing is not fully investigated. Stimulation of bronchial epithelial cells (BECs) with tryptase promoted gap closure, migration and cellular speed compared to controls. Stimulated BECs had higher expression of migration marker CD151 compared to controls. Proliferation marker KI67 was upregulated in tryptase-stimulated BECs compared to controls. Treatment with PAR2 antagonist I-191 reduced gap closure, migration and cell speed compared to BECs stimulated with tryptase. We found that tryptase enhances epithelial wound healing by increased migration and proliferation, which is in part regulated via PAR2. Our data suggest that tryptase might be beneficial in tissue repair under baseline conditions. However, in a pathological context such as asthma with increased numbers of activated MCs, it might lead to epithelial remodeling and loss of function.
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| 3. |
- Zwedberg, Sofia, et al.
(författare)
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Midwives' experiences as preceptors and the development of good preceptorships in obstetric units
- 2020
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Ingår i: Midwifery. - : Elsevier BV. - 0266-6138 .- 1532-3099. ; 87
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study midwives' experience in their role as a preceptor and their perception on how to best support midwifery students in obstetrics units. Obstetric units are an important learning area for student midwives but knowledge on how to become a good midwife preceptor is limited. Design: This qualitative study explores midwife preceptors' experience of supervising midwifery students in three obstetric units in Sweden. Following ethical approval seventeen midwife preceptors were inter- viewed and data were analysed thematically. Findings: Thematic analysis of the interviews resulted in the identification of two themes and five sub- themes: (1) self-efficacy in the preceptor role which involves (a) being confident in the professional posi- tion and (b) having the support of management and colleagues and (2) supporting the student to attain self-confidence and independence which entails (a) helping the student to grow, (b) facilitating reflection in learning situations, and (c) "taking a step back". Key conclusion: Good preceptorship occurs when midwives achieve full self-efficacy, when they master the preceptor role, and when they have enhanced their abilities to help, the student reach confidence and independence. Implications for practice: Health care organisations needs to develop and support midwifery preceptor- ships
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| 4. |
- Södergren, Anna, et al.
(författare)
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Responsiveness of platelets during storage studied with flow cytometry - formation of platelet subpopulations and LAMP-1 as new markers for the platelet storage lesion
- 2016
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Ingår i: Vox Sanguinis. - : Wiley-Blackwell Publishing Inc.. - 0042-9007 .- 1423-0410. ; 110:2, s. 116-125
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Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectivesStorage lesions may prevent transfused platelets to respond to agonists and arrest bleeding. The aim of this study was to evaluate and quantify the capacity of platelet activation during storage using flow cytometry and new markers of platelet activation. Materials and MethodsActivation responses of platelets prepared by apheresis were measured on days 1, 5, 7 and 12. In addition, comparisons were made for platelet concentrates stored until swirling was affected. Lysosome-associated membrane protein-1 (LAMP-1), P-selectin and phosphatidylserine (PS) exposure were assessed by flow cytometry on platelets in different subpopulations in resting state or following stimulation with platelet agonists (cross-linked collagen-related peptide (CRP-XL), PAR1- and PAR4-activating peptides). ResultsThe ability to form subpopulations upon activation was significantly decreased already at day 5 for some agonist combinations. The agonist-induced exposure of PS and LAMP-1 also gradually decreased with time. Spontaneous exposure of P-selectin and PS increased with time, while spontaneous LAMP-1 exposure was unchanged. In addition, agonist-induced LAMP-1 expression clearly discriminated platelet concentrates with reduced swirling from those with retained swirling. This suggests that LAMP-1 could be a good marker to capture changes in activation capacity in stored platelets. ConclusionThe platelet activation potential seen as LAMP-1 exposure and fragmentation into platelet subpopulations is potential sensitive markers for the platelet storage lesion.
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| 5. |
- Berlin, Frida, et al.
(författare)
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Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells
- 2023
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Ingår i: Cells. - 2073-4409. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Bronchial and alveolar remodeling and impaired epithelial function are characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells (MCs) positive for serine proteases, tryptase and chymase, infiltrate the epithelium and alveolar parenchyma. However, little is known regarding the implication of intraepithelial MCs on the local environment, such as epithelial cell function and properties. In this study, we investigated whether MC tryptase is involved in bronchial and alveolar remodeling and the mechanisms of regulation during inflammation. Using novel holographic live cell imaging, we found that MC tryptase enhanced human bronchial and alveolar epithelial cell growth and shortened the cell division intervals. The elevated cell growth induced by tryptase remained in a pro-inflammatory state. Tryptase also increased the expression of the anti-apoptotic protein BIRC3, as well as growth factor release in epithelial cells. Thus, our data imply that the intraepithelial and alveolar MC release of tryptase may play a critical role in disturbing bronchial epithelial and alveolar homeostasis by altering cell growth–death regulation.
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| 6. |
- Callesen, Katrine T., et al.
(författare)
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Characterization of Mast Cells from Healthy and Varicose Human Saphenous Vein
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells (MCs) are distributed in tissues throughout the body and are highly involved in many physiological and pathophysiological processes. The potential and involvement of different MC phenotypes are still not well understood. MCs are present in blood vessel walls, but their specific phenotypic features are unknown. We aimed at characterizing MCs from human saphenous veins for localization, mediator content, and receptor expression. This was done in MCs from both healthy and varicose human saphenous veins (hSV and vSV, respectively). For both vSV and hSV, we found that vein MCs are mainly present in the tunica adventitia (99% MCs in adventitia) and that the population consists of both MCT and MCTC phenotypes (vSV: 55% MCT, hSV: 64% MCT). The vein MCs contained high levels of histamine (vSV: 27 pg/MC, hSV: 55 pg/MC) and tryptase (vSV: 98 pg/MC, hSV: 111 pg/MC), indicating a strong potential for regulatory effects on blood vessels. The receptor expression of FcɛRI, MRGPRX2, PTAFR, C3aR, and C5aR was found, even though the percentage of positive cells differed between vSV and hSV MCs. We conclude that vein MCs from the blood vessel wall have a high potential to affect the tissue around them.
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| 7. |
- Klingberg, Gunilla, et al.
(författare)
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How old are you? : a systematic review investigating the relationship between age and mandibular third molar maturity
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:5, s. 1-14
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Forskningsöversikt (refereegranskat)abstract
- Introduction and objective: Radiographic evaluation of the maturity of mandibular third molars is a common method used for age estimation of adolescents and young adults. The aim of this systematic review was to examine the scientific base for the relationship between a fully matured mandibular third molar based on Demirjian's method and chronological age, in order to assess whether an individual is above or below the age of 18 years.Methods: The literature search was conducted in six databases until February 2022 for studies reporting data evaluating the tooth maturity using Demirjian´s method (specifically stage H) within populations ranging from 8 to 30 years (chronological age). Two reviewers screened the titles and abstracts identified through the search strategy independently. All studies of potential relevance according to the inclusion criteria were obtained in full text, after which they were assessed for inclusion by two independent reviewers. Any disagreement was resolved by a discussion. Two reviewers independently evaluated the risk of bias using the assessment tool QUADAS-2 and extracted the data from the studies with low or moderate risk of bias. Logistic regression was used to estimate the relationship between chronological age and proportion of subjects with a fully matured mandibular third molar (Demirjian´s tooth stage H).Results: A total of 15 studies with low or moderate risk of bias were included in the review. The studies were conducted in 13 countries and the chronological age of the investigated participants ranged from 3 to 27 years and the number of participants ranged between 208 and 5,769. Ten of the studies presented the results as mean age per Demirjian´s tooth stage H, but only five studies showed the distribution of developmental stages according to validated age. The proportion of subjects with a mandibular tooth in Demirjian´s tooth stage H at 18 years ranged from 0% to 22% among males and 0 to 16% in females. Since the studies were too heterogenous to perform a meta-analysis or a meaningful narrative review, we decided to refrain from a GRADE assessment.Conclusion: The identified literature does not provide scientific evidence for the relationship between Demirjian´s stage H of a mandibular third molar and chronologic age in order to assess if an individual is under or above the age of 18 years.
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| 8. |
- Mogren, Sofia, et al.
(författare)
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Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:18
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Tidskriftsartikel (refereegranskat)abstract
- Tissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor, urokinase plasminogen activator receptor (uPAR), has been shown to regulate bronchial epithelial repair responses. However, the impact of MC tryptase and chymase on functional properties and expression of uPAR in alveolar epithelial cells have not been fully investigated. Alveolar epithelial cell migration and wound healing were investigated using holographic live cell imaging of A549 cells in a wound scratch model post stimulation with tryptase or chymase. The expression of uPAR was investigated on the protein and gene level from cellular supernatants and in bronchoalveolar lavage fluid fractions from allergic asthmatics. We found that tryptase improved wound healing capacity, cellular migration and membrane bound uPAR expression. Chymase reduced gap closure capacity, cellular migration and membrane bound uPAR expression but increased soluble uPAR release. Our data suggest a dual regulatory response from the MC proteases in events related to uPAR expression and wound healing which could be important features in asthmatic disease.
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| 9. |
- Nordström, Erik
(författare)
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Samordnad individuell plan (SIP) : Professionellas samt barn och föräldrars erfarenheter
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduktion. Många barn och unga idag har så pass komplexa behov att de behöver samtidiga insatser från olika huvudmän. Insatserna blir alltmer specialiserade och fragmenterade, vilket kräver att professioner inom hälso- och sjukvård, socialtjänst och skola samverkar. Det finns också ett lagstiftat krav sedan 2010 på samverkan i form av Samordnad individuell plan (SIP). SIP möjliggör för barn och föräldrar att få överblick och få samordnade insatser av hälso- och sjukvården och socialtjänsten genom möte, planering och dokumenterade insatser.Syftet med avhandlingen var att beskriva professionellas, barn och föräldrars erfarenhet av samordnad individuell plan (SIP).Design och metod. Två deskriptiva studier genomfördes i ett län i södra Sverige. Delstudie 1 bestod av tolv fokusgruppsintervjuer med sammanlagt 71 personer med olika yrkeskategorier inom hälso- och sjukvården, socialtjänsten och skolan. Delstudie 2 bestod av semi-strukturerade intervjuer med sammantaget tretton barn och föräldrar från olika familjer. Bägge studierna analyserades med kvalitativ metod.Resultat. Resultatet i delstudie 1 visar att verksamheterna gör en primär avvägning mellan samverkan och sitt respektive kärnuppdrag; vårdande, pedagogisk och utredande. Samverkan skedde genom en pendling mellan hindrande och främjande faktorer. Hindrande faktorer består av olika mandat och behov, tvång till närvaro, ifrågasättande och klander, samt tidsramar och prioriteringar. Främjande faktorer är likartad tolkning av gemensamma avtal, ömsesidig respektoch kollegialt lärande, gemensam terminologi och dokumentation, samt intresse för samverkan. Delstudie 2 visar att barn och föräldrars upplevelse av delaktighet i form av SIP ökade över tid och att de över tid upplevde att de fick ett samordnat stöd från olika vårdgivare, som barnen och/eller föräldrarna innan SIP ofta själva fick samordna. Detta mål uppnåddes först efter initialt motstånd och konkurrens mellan olika verksamheter, och det underlättade att skapa relationer och allianser med professionella för att nå detta mål. Resultatet diskuteras utifrån fyra olika stadier av samverkan och förutsättningar för att intentionerna med SIP avseende delaktighet skall uppnås.Konklusion och praktiska implikationer. SIP tycks ha potential att bidra till en förbättrad samverkan om de professionella visar ömsesidig kollegial respekt och har fokus på barn och föräldrars behov. Detta kan lättare uppnås om professionella inte lägger för stor vikt vid skydda den egna verksamhetens agenda istället för en samverkansagenda. Detta bekräftas av delstudie 2 som visar att barn och föräldrar uppfattar att det finns intentioner att göra brukaren delaktig, men att denna intention hindras av oenighet, skilda intentioner och bristande samsyn mellan verksamheter, och barn och föräldrar får utstå förvirring och fragmentering av insatserna under lång tid, vilket kan utsätta barnet för risker. Om SIP skall bli det verktyg för helhetslösning och brukardelaktighet som det är avsett att vara, så behöver de berörda professionerna uppnå en bredare samsyn kring SIP för att uppfylla intentionen med en samverkan med utökad brukardelaktighet.
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| 10. |
- Ramu, Sangeetha, et al.
(författare)
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Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses
- 2021
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Ingår i: BMC Immunology. - : Springer Science and Business Media LLC. - 1471-2172. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mast cells (MCs) are known to contribute to both acute and chronic inflammation. Bronchial epithelial cells are the first line of defence against pathogens and a deficient anti-viral response has been suggested to play a role in the pathogenesis of asthma exacerbations. However, effects of MC mediators on bronchial epithelial immune response have been less studied. The aim of this study is to investigate the direct effects of stimulation with MC proteases, tryptase and chymase, on inflammatory and anti-viral responses in human bronchial epithelial cells (HBECs). Method: Cultured BEAS-2b cells and primary HBECs from 3 asthmatic patients were stimulated with tryptase or chymase (0.1 to 0.5 μg/ml) for 1, 3, 6 and 24 h. To study the effects of MC mediators on the anti-viral response, cells were stimulated with 10 μg/ml of viral mimic Poly (I:C) for 3 and 24 h following pre-treatment with 0.5 μg/ml tryptase or chymase for 3 h. Samples were analysed for changes in pro-inflammatory and anti-viral mediators and receptors using RT-qPCR, western blot and Luminex. Results: Tryptase and chymase induced release of the alarmin ATP and pro-inflammatory mediators IL-8, IL-6, IL-22 and MCP-1 from HBECs. Moreover, tryptase and chymase decreased the expression of E-cadherin and zonula occludens-1 expression from HBECs. Pre-treatment of HBECs with tryptase and chymase further increased Poly (I:C) induced IL-8 release at 3 h. Furthermore, tryptase significantly reduced type-I and III interferons (IFNs) and pattern recognition receptor (PRR) expression in HBECs. Tryptase impaired Poly (I:C) induced IFN and PRR expression which was restored by treatment of a serine protease inhibitor. Similar effects of tryptase on inflammation and anti-viral responses were also confirmed in primary HBECs from asthmatic patients. Conclusion: MC localization within the epithelium and the release of their proteases may play a critical role in asthma pathology by provoking pro-inflammatory and alarmin responses and downregulating IFNs. Furthermore, MC proteases induce downregulation of epithelial junction proteins which may lead to barrier dysfunction. In summary, our data suggests that mast cells may contribute towards impaired anti-viral epithelial responses during asthma exacerbations mediated by the protease activity of tryptase.
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