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Christian H. Lindh - One of the best experts on this subject based on the ideXlab platform.
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comprehensive proteome analysis of Nasal Lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor lxr rxr activation that influence the status of the extracellular matrix
2018Co-Authors: Neserin Ali, Jørn Nielsen, Jenny Rissler, Helen Karlsson, Anders Gudmundsson, Stefan Ljunggren, Aneta Wierzbicka, Joakim Pagels, Christina Isaxon, Christian H. LindhAbstract:Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in Nasal Lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal Lavage samples were collected before, immediately after, and the day after exposure. The proteins in the Nasal Lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC–MS/MS and a targeted selected reaction monitoring LC–MS/MS analyzing 130 proteins and four in vivo peptide degradation products. The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in Nasal Lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.
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analysis of nanoparticle protein coronas formed in vitro between nanosized welding particles and Nasal Lavage proteins
2016Co-Authors: Neserin Ali, Christian H. Lindh, Karin Mattsson, Jenny Rissler, Helen Karlsson, Christian Svensson, Anders Gudmundsson, Bo A G Jonsson, Tommy Cedervall, Monica KåredalAbstract:Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich Nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between Nasal Lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When Nasal Lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when Nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant Nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
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Targeted Proteomic Analyses of Nasal Lavage Fluid in Persulfate-Challenged Hairdressers with Bleaching Powder-Associated Rhinitis
2015Co-Authors: Harriet Mörtstedt, Neserin Ali, Monica Kåredal, Helene Jacobsson, Emelie Rietz, Kerstin Kronholm Diab, Jörn Nielsen, Bo A.g. Jönsson, Christian H. LindhAbstract:Hairdressers have an increased risk for developing airway symptoms, for example, asthma and rhinitis. Persulfates, which are oxidizing agents in bleaching powder, are considered important causal agents for these symptoms. However, the underlying mechanisms are unclear. The aim was therefore to measure proteomic changes in Nasal Lavage fluid from persulfate-challenged subjects to identify proteins potentially involved in the pathogenesis of bleaching powder-associated rhinitis or candidate effect biomarkers for persulfate. Also, oxidized peptides were measured to evaluate their usefulness as biomarkers for persulfate exposure or effect, for example, oxidative stress. Samples from hairdressers with and without bleaching powder-associated rhinitis were analyzed with liquid chromatography tandem mass spectrometry using selected reaction monitoring to target 246 proteins and five oxidized peptides. Pathway analysis was applied to obtain a functional overview of the proteins. Several proteins involved in biologically meaningful pathways, functions, or disorders, for example, inflammatory responses, oxidative stress, epithelium integrity, and dermatological disorders, changed after the persulfate challenge. A list with nine proteins that appeared to be affected by the persulfate challenge and should be followed up was defined. An albumin peptide containing oxidized tryptophan increased 2 h and 5 h after the challenge but not after 20 min, which indicates that such peptides may be useful as oxidative stress biomarkers
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Screening Method Using Selected Reaction Monitoring for Targeted Proteomics Studies of Nasal Lavage Fluid.
2012Co-Authors: Harriet Mörtstedt, Monica Kåredal, Bo Jönsson, Christian H. LindhAbstract:Proteomic-based studies of Nasal Lavage fluid (NLF) may identify molecular pathways associated with disease pathology and new biomarker candidates of upper airway diseases. However, most studies have used rather tedious untargeted MS techniques. Selected reaction monitoring (SRM) is a sensitive and specific technique that can be used with high throughput. In this study, we developed a semiquantitative SRM-based method targeting 244 NLF proteins. The protein set was identified through a literature study in combination with untargeted LC–MS/MS analyses of trypsin-digested NLF samples. The SRM assays were designed using MS/MS data either downloaded from a proteomic data repository or experimentally obtained. Each protein is represented by one to five peptides, resulting in 708 SRM assays. Three to four transitions per assay were used to ensure analyte specificity. The majority (69%) of the assays showed good within-day precision (coefficient of variation ≤20%). The accuracy of the method was evaluated by ana...
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Time-Dependent Proteomic iTRAQ Analysis of Nasal Lavage of Hairdressers Challenged by Persulfate
2010Co-Authors: Monica H. Kåredal, Bo A.g. Jönsson, Kerstin Kronholm Diab, Jørn Nielsen, Christian H. LindhAbstract:Hairdressers are frequently exposed to bleaching powder containing persulfates, a group of compounds that may induce hypersensitivity in the airways. The mechanism causing this reaction is not clear. The aim of this study was to identify changes in the Nasal Lavage fluid proteome after challenge with potassium persulfate in hairdressers with bleaching powder-associated rhinitis. Furthermore, we aimed to compare their response to that of hairdressers without Nasal symptoms, and atopic subjects with pollen-associated Nasal symptoms. To study the pathogenesis of persulfate-associated rhinitis, the response in protein expression from the upper airway was assessed by time-dependent proteomic expression analysis of Nasal Lavage fluids. Samples were prepared by pooling Nasal Lavage fluids from the groups at different time points after challenge. Samples were depleted of high-abundant proteins, labeled with iTRAQ and analyzed by online 2D-nanoLC-MS/MS. Differences in the protein pattern between the three groups were observed. Most proteins with differentially expressed levels were involved in pathways of lipid transportation and antimicrobial activities. The major finding was increased abundance of apolipoprotein A-1, 20 min postchallenge, detected solely in the group of symptomatic hairdressers. Our results suggest there may be differences between the mechanisms responsible for the rhinitis in the symptomatic and atopic group
Mats Lindahl - One of the best experts on this subject based on the ideXlab platform.
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protein profiles of Nasal Lavage fluid from individuals with work related upper airway symptoms associated with moldy and damp buildings
2016Co-Authors: Karin Wåhlén, Louise Fornander, Patrik Olausson, Kjell Ydreborg, Ulf Flodin, Pål Graff, Mats Lindahl, Bijar GhafouriAbstract:Upper airway irritation is common among individuals working in moldy and damp buildings. The aim of this study was to investigate effects on the protein composition of the Nasal lining fluid. The prevalence of symptoms in relation to work environment was examined in 37 individuals working in two damp buildings. Microbial growth was confirmed in one of the buildings. Nasal Lavage fluid was collected from 29 of the exposed subjects and 13 controls, not working in a damp building. Protein profiles were investigated with a proteomic approach and evaluated by multivariate statistical models. Subjects from both workplaces reported upper airway and ocular symptoms. Based on protein profiles, symptomatic subjects in the two workplaces were discriminated from each other and separated from healthy controls. The groups differed in proteins involved in inflammation and host defense. Measurements of innate immunity proteins showed a significant increase in protein S100-A8 and decrease in SPLUNC1 in subjects from one workplace, while alpha-1-antitrypsin was elevated in subjects from the other workplace, compared with healthy controls. The results show that protein profiles in Nasal Lavage fluid can be used to monitor airway mucosal effects in personnel working in damp buildings and indicate that the profile may be separated when the dampness is associated with the presence of molds.
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airway symptoms and biological markers in Nasal Lavage fluid in subjects exposed to metalworking fluids
2013Co-Authors: Louise Fornander, Karin Wåhlén, Kjell Ydreborg, Ulf Flodin, Pål Graff, Mats Lindahl, Per Leanderson, Bijar GhafouriAbstract:Backgrounds: Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in Nasal mucous membranes, and evaluate preventive actions. Methods: The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal Lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach. Results: Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and b2-microglobulin among workers with airway symptoms. Conclusions: This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.
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PLUNC in human Nasal Lavage fluid: multiple isoforms that bind to lipopolysaccharide.
2004Co-Authors: Bijar Ghafouri, Erik Kihlström, Christer Tagesson, Mats LindahlAbstract:Here, we demonstrate the presence of multiple isoforms of palate lung Nasal epithelial clone (PLUNC) in human Nasal Lavage fluid (NLF). Eight isoforms were separated by two-dimensional gel electrophoresis (2-DE), and peptide mapping of the proteins was performed using MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry) of tryptic and asparginase cleavages. The identification was verified by amino acid sequencing after analysis of collision-induced dissociation (CID) fragmentation spectra with nanoelectrospray MS/MS. One isoform showed an electrophoretic mobility shift after N-glycosidase treatment, indicating that at least one of the PLUNC isoforms is glycosylated. We also demonstrate that PLUNC in NLF binds to lipopolysaccharide (LPS) in vitro; indeed, out of all proteins present in NLF only the PLUNC isoforms were found to adsorb to an LPS-coated surface. These results show that PLUNC is expressed as multiple LPS-binding isoforms in human NLF. The possibility that PLUNC may play a role in the innate immune response of the upper airways is inferred.
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Nasal Lavage fluid and proteomics as means to identify the effects of the irritating epoxy chemical dimethylbenzylamine
2004Co-Authors: Mats Lindahl, Christer Tagesson, Kristina Irander, B StåhlbomAbstract:The aims of this study were to describe the changes in the Nasal Lavage fluid (NLF) protein pattern after exposure to the irritating epoxy chemical dimethylbenzylamine (DMBA) and to identify the affected proteins using a proteomic approach. The protein patterns of NLF from six healthy subjects and eight epoxy workers with airway irritation were analysed using two-dimensional gel electrophoresis (2-DE) before and after exposure to 100 μg m-3 DMBA for 2 h in an exposure chamber. NLF proteins were identified by (i) comparison with a 2-DE NLF reference database, (ii) N-terminal amino acid sequencing, and (iii) mass spectrometry. In NLF from healthy subjects, the levels of immunoglobulin A increased and the levels of Clara cell protein 16 (CC16) decreased after chamber exposure, while in NLF from epoxy workers, α2-macroglobulin and caeruloplasmin increased. Two previously unidentified proteins decreased in NLF from epoxy workers after exposure, these were identified as statherin and calgranulin B. In addition, the subjects who developed high counts of eosinophils in their Nasal mucosa after chamber exposure had significantly lower levels of immunoglobulin-binding factor (IgBF) before exposure than subjects with low eosinophil infiltration. These results show that short-term exposure to DMBA causes distinct changes in NLF proteins. Moreover, three proteins that have previously not been associated with upper airway irritation were identified: statherin, calgranulin B and IgBF. Further studies are needed to investigate whether these proteins may be used as biomarkers of airway irritation and to give new insight into the ways in which occupational exposure to irritants causes inflammation of the airways.
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PLUNC (palate, lung and Nasal epithelial clone) proteins in human Nasal Lavage fluid
2003Co-Authors: Bijar Ghafouri, Erik Kihlström, Christer Tagesson, B Ståhlbom, Mats LindahlAbstract:PLUNC (palate, lung and Nasal epithelial clone) is a newly discovered gene that is expressed in the upper respiratory tract and is suggested to be of importance in host defence against bacteria. We have identified two forms of the PLUNC protein in human Nasal Lavage fluid (NLF) using two-dimensional gel electrophoresis (2-DE) and MS. The apparent molecular masses and isoelectric points of these forms are 24.8 kDa/pI 5.4 and 25.1 kDa/pI 5.5. Notably, the 24.8 kDa/pI 5.4 form of PLUNC is an abundant protein in the 2-DE protein patterns of NLF from healthy subjects. Decreased levels of PLUNC were found in NLF from smokers and workers exposed to reactive epoxy chemicals, indicating that long-term exposure to airway irritants impairs the production of PLUNC in the upper respiratory tract. We have also investigated the presence of lipopolysaccharide (LPS)-binding proteins in NLF. Five proteins were found to adsorb to a LPS-coated surface; two of these proteins correspond to the two PLUNC forms, as judged by 2-DE pattern matching. For comparison, human saliva was found to contain a set of LPS-binding proteins with similar 2-DE spot positions (the same pIs but somewhat lower apparent molecular masses of ≈20 kDa). These results indicate that PLUNC may be a new marker of airway inflammation and may play a part in the innate immune response, and that human saliva contains yet other members of the family of LPS-binding proteins.
Maija-riitta Hirvonen - One of the best experts on this subject based on the ideXlab platform.
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The effect of assay type and sample matrix on detected cytokine concentrations in human blood serum and Nasal Lavage fluid.
2014Co-Authors: Kati Huttunen, Kati Tiihonen, Marjut Roponen, Dick Heederik, Jan Paul Zock, Martin Täubel, Anne Hyvärinen, Maija-riitta HirvonenAbstract:Cytokine concentrations in biological fluids are widely used markers for activation of immunological processes. Confirming the reproducibility of measurements is important, especially in longitudinal or multicenter studies where time between analyses or different analyzing laboratories increases the intra-assay variability. In this study, the reproducibility of the cytokine analysis conducted with different assay platforms was studied by comparing the results of two cytokines [interleukin (IL)-6 in serum and Nasal Lavage fluid (NAL) and IL-8 in NAL] analyzed with Meso Scale Discovery (MSD) ultra-sensitive single and multiplex assay kits (n=76). In addition, the difference in cytokine levels between two biological sample matrices was studied by comparing the results of altogether 9 cytokines [IL-6, IL-2, IL-8, IL12p70, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)γ, IL-10 and tumor necrosis factor (TNF)α] measured from serum and NAL of the same study subjects (n=460). The results show that the cytokine concentrations analyzed with single and multiplex assays are concordant but not equal. Comparison of the different matrices revealed that cytokine concentrations in serum do not correspond with concentrations detected in Nasal Lavage fluid. It can be concluded that comparability of the results from single and multiplex analysis of cytokines is high, but the concentrations should not be compared directly with each other. The differences between concentrations analyzed from serum and Nasal Lavage fluid indicate that the levels are specific for each matrix and represent distinct immunological conditions.
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microbial exposure symptoms and inflammatory mediators in Nasal Lavage fluid of kitchen and clerical personnel in schools
2005Co-Authors: Ulla Lignell, Marjut Roponen, Maija-riitta Hirvonen, Teija Meklin, Tuula Putus, Asko Vepsalainen, Eila Torvinen, Morten Reeslev, Sirpa Pennanen, Pentti KalliokoskiAbstract:Objectives: The aim of this study was to investigate how the microbial conditions of kitchen facilities differ from those in other school facilities. The health status of the personnel was also studied. Materials and Methods: The microbial investigations were conducted in six moisture-damaged schools and two reference schools. The symptoms of the kitchen personnel were surveyed with questionnaires and inflammatory responses in Nasal Lavage (NAL) fluid were measured. Results: The total concentrations of airborne microbes were lower in kitchens than in other facilities of the schools. However, the occurrence of moisture damage increased the airborne microbial concentrations both in kitchens, and in other facilities. Bacterial concentrations were high on surfaces in the damaged kitchens. Gram-negative bacteria predominated, but also thermophilic bacteria and mycobacteria were detected. Respiratory and general symptoms were prevalent both among kitchen workers and clerical personnel in the moisture-damaged environments. Reported allergies and repeated respiratory infections were connected with high IL-4 concentrations in NAL fluid. Median concentrations of studied inflammatory mediators (NO, IL-4, IL-6 and TNF-a) were slightly higher in NAL samples of kitchen workers than among the clerical personnel. Conclusions: Kitchen facilites differ from other facilities of the school building for their moisture conditions and microbial contamination. Thus, they represent a specific type of environment that may affect the health status of the personnel.
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Nasal Lavage method in the monitoring of upper airway inflammation seasonal and individual variation
2003Co-Authors: Marjut Roponen, Aino Nevalainen, Markku Seuri, Jukka Randell, Maija-riitta HirvonenAbstract:A noninvasive and reliable method is needed to investigate causal relationship between exposure to bioaerosols in occupational and indoor environments and adverse health effects. As an essential part of the method development, the individual variation as well as seasonal and gender differences in the concentrations of inflammatory mediators in Nasal Lavage (NAL) fluid were studied. NAL was performed in 10 healthy volunteers every other week for a year. Concentrations of nitric oxide, assessed as nitrite, interleukin (IL)-1 beta, IL-4, IL-5, IL-6, and tumor necrosis factor alpha (TNF alpha) in NAL fluid were measured. The NAL sampling was minimally invasive and well tolerated and no side effects were observed among the studied subjects. Low concentrations of nitrite, TNFalpha, IL-1 beta, IL-4, and IL-6 were detected in the NAL samples of the studied subjects. Within-subject variation in the concentrations of inflammatory mediators in the NAL fluid was at its lowest during the wintertime. Moreover, differences between individuals and genders were statistically significant. In summary, the individual variation in the basal levels of measured inflammatory markers is low, whereas differences between individuals are considerable. Thus, in the studies evaluating upper airway effects of occupational or environmental exposure, the method is most suitable in settings where comparison can be made using test subjects as their own controls.
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Nitric oxide and proinflammatory cytokines in Nasal Lavage fluid associated with symptoms and exposure to moldy building microbes
1999Co-Authors: Maija-riitta Hirvonen, Marjut Roponen, Anne Hyvärinen, Marjo Ruotsalainen, Tuula Husman, Veli-matti Kosma, Hannu Komulainen, Kai Savolainen, Aino NevalainenAbstract:Epidemiological data indicate that living or working in a moldy building is associated with increased risk of respiratory symptoms and disease related to inflammatory reactions, but biochemical evidence linking cause and effect is still scarce. The staff working in a mold-contaminated school, and a reference group without such exposure, were studied. Nasal Lavage was performed and health data were collected with a questionnaire at the end of the spring term, after a 2.5-mo summer vacation, and at the end of the fall term. Here we show that concentrations of tumor necrosis factor alpha (TNF- α ), interleukin-6 (IL-6), and nitric oxide (NO) in Nasal Lavage fluid were significantly higher in the exposed than in the control subjects at the end of the first exposure period. These inflammatory mediators decreased to reference group concentrations during the period when there was no exposure and the production of NO and IL-6 increased again during the reexposure in the fall term. Reports of cough, phlegm, rhinit...
Bijar Ghafouri - One of the best experts on this subject based on the ideXlab platform.
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protein profiles of Nasal Lavage fluid from individuals with work related upper airway symptoms associated with moldy and damp buildings
2016Co-Authors: Karin Wåhlén, Louise Fornander, Patrik Olausson, Kjell Ydreborg, Ulf Flodin, Pål Graff, Mats Lindahl, Bijar GhafouriAbstract:Upper airway irritation is common among individuals working in moldy and damp buildings. The aim of this study was to investigate effects on the protein composition of the Nasal lining fluid. The prevalence of symptoms in relation to work environment was examined in 37 individuals working in two damp buildings. Microbial growth was confirmed in one of the buildings. Nasal Lavage fluid was collected from 29 of the exposed subjects and 13 controls, not working in a damp building. Protein profiles were investigated with a proteomic approach and evaluated by multivariate statistical models. Subjects from both workplaces reported upper airway and ocular symptoms. Based on protein profiles, symptomatic subjects in the two workplaces were discriminated from each other and separated from healthy controls. The groups differed in proteins involved in inflammation and host defense. Measurements of innate immunity proteins showed a significant increase in protein S100-A8 and decrease in SPLUNC1 in subjects from one workplace, while alpha-1-antitrypsin was elevated in subjects from the other workplace, compared with healthy controls. The results show that protein profiles in Nasal Lavage fluid can be used to monitor airway mucosal effects in personnel working in damp buildings and indicate that the profile may be separated when the dampness is associated with the presence of molds.
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airway symptoms and biological markers in Nasal Lavage fluid in subjects exposed to metalworking fluids
2013Co-Authors: Louise Fornander, Karin Wåhlén, Kjell Ydreborg, Ulf Flodin, Pål Graff, Mats Lindahl, Per Leanderson, Bijar GhafouriAbstract:Backgrounds: Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in Nasal mucous membranes, and evaluate preventive actions. Methods: The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal Lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach. Results: Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and b2-microglobulin among workers with airway symptoms. Conclusions: This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.
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PLUNC in human Nasal Lavage fluid: multiple isoforms that bind to lipopolysaccharide.
2004Co-Authors: Bijar Ghafouri, Erik Kihlström, Christer Tagesson, Mats LindahlAbstract:Here, we demonstrate the presence of multiple isoforms of palate lung Nasal epithelial clone (PLUNC) in human Nasal Lavage fluid (NLF). Eight isoforms were separated by two-dimensional gel electrophoresis (2-DE), and peptide mapping of the proteins was performed using MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry) of tryptic and asparginase cleavages. The identification was verified by amino acid sequencing after analysis of collision-induced dissociation (CID) fragmentation spectra with nanoelectrospray MS/MS. One isoform showed an electrophoretic mobility shift after N-glycosidase treatment, indicating that at least one of the PLUNC isoforms is glycosylated. We also demonstrate that PLUNC in NLF binds to lipopolysaccharide (LPS) in vitro; indeed, out of all proteins present in NLF only the PLUNC isoforms were found to adsorb to an LPS-coated surface. These results show that PLUNC is expressed as multiple LPS-binding isoforms in human NLF. The possibility that PLUNC may play a role in the innate immune response of the upper airways is inferred.
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PLUNC (palate, lung and Nasal epithelial clone) proteins in human Nasal Lavage fluid
2003Co-Authors: Bijar Ghafouri, Erik Kihlström, Christer Tagesson, B Ståhlbom, Mats LindahlAbstract:PLUNC (palate, lung and Nasal epithelial clone) is a newly discovered gene that is expressed in the upper respiratory tract and is suggested to be of importance in host defence against bacteria. We have identified two forms of the PLUNC protein in human Nasal Lavage fluid (NLF) using two-dimensional gel electrophoresis (2-DE) and MS. The apparent molecular masses and isoelectric points of these forms are 24.8 kDa/pI 5.4 and 25.1 kDa/pI 5.5. Notably, the 24.8 kDa/pI 5.4 form of PLUNC is an abundant protein in the 2-DE protein patterns of NLF from healthy subjects. Decreased levels of PLUNC were found in NLF from smokers and workers exposed to reactive epoxy chemicals, indicating that long-term exposure to airway irritants impairs the production of PLUNC in the upper respiratory tract. We have also investigated the presence of lipopolysaccharide (LPS)-binding proteins in NLF. Five proteins were found to adsorb to a LPS-coated surface; two of these proteins correspond to the two PLUNC forms, as judged by 2-DE pattern matching. For comparison, human saliva was found to contain a set of LPS-binding proteins with similar 2-DE spot positions (the same pIs but somewhat lower apparent molecular masses of ≈20 kDa). These results indicate that PLUNC may be a new marker of airway inflammation and may play a part in the innate immune response, and that human saliva contains yet other members of the family of LPS-binding proteins.
Neserin Ali - One of the best experts on this subject based on the ideXlab platform.
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comprehensive proteome analysis of Nasal Lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor lxr rxr activation that influence the status of the extracellular matrix
2018Co-Authors: Neserin Ali, Jørn Nielsen, Jenny Rissler, Helen Karlsson, Anders Gudmundsson, Stefan Ljunggren, Aneta Wierzbicka, Joakim Pagels, Christina Isaxon, Christian H. LindhAbstract:Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in Nasal Lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal Lavage samples were collected before, immediately after, and the day after exposure. The proteins in the Nasal Lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC–MS/MS and a targeted selected reaction monitoring LC–MS/MS analyzing 130 proteins and four in vivo peptide degradation products. The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in Nasal Lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.
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analysis of nanoparticle protein coronas formed in vitro between nanosized welding particles and Nasal Lavage proteins
2016Co-Authors: Neserin Ali, Christian H. Lindh, Karin Mattsson, Jenny Rissler, Helen Karlsson, Christian Svensson, Anders Gudmundsson, Bo A G Jonsson, Tommy Cedervall, Monica KåredalAbstract:Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich Nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between Nasal Lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When Nasal Lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when Nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant Nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
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Targeted Proteomic Analyses of Nasal Lavage Fluid in Persulfate-Challenged Hairdressers with Bleaching Powder-Associated Rhinitis
2015Co-Authors: Harriet Mörtstedt, Neserin Ali, Monica Kåredal, Helene Jacobsson, Emelie Rietz, Kerstin Kronholm Diab, Jörn Nielsen, Bo A.g. Jönsson, Christian H. LindhAbstract:Hairdressers have an increased risk for developing airway symptoms, for example, asthma and rhinitis. Persulfates, which are oxidizing agents in bleaching powder, are considered important causal agents for these symptoms. However, the underlying mechanisms are unclear. The aim was therefore to measure proteomic changes in Nasal Lavage fluid from persulfate-challenged subjects to identify proteins potentially involved in the pathogenesis of bleaching powder-associated rhinitis or candidate effect biomarkers for persulfate. Also, oxidized peptides were measured to evaluate their usefulness as biomarkers for persulfate exposure or effect, for example, oxidative stress. Samples from hairdressers with and without bleaching powder-associated rhinitis were analyzed with liquid chromatography tandem mass spectrometry using selected reaction monitoring to target 246 proteins and five oxidized peptides. Pathway analysis was applied to obtain a functional overview of the proteins. Several proteins involved in biologically meaningful pathways, functions, or disorders, for example, inflammatory responses, oxidative stress, epithelium integrity, and dermatological disorders, changed after the persulfate challenge. A list with nine proteins that appeared to be affected by the persulfate challenge and should be followed up was defined. An albumin peptide containing oxidized tryptophan increased 2 h and 5 h after the challenge but not after 20 min, which indicates that such peptides may be useful as oxidative stress biomarkers
