| 1. |
|
|
| 2. |
- Abolhalaj, Milad, et al.
(författare)
-
Profiling dendritic cell subsets in head and neck squamous cell tonsillar cancer and benign tonsils.
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:8030
-
Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) have a key role in orchestrating immune responses and are considered important targets for immunotherapy against cancer. In order to develop effective cancer vaccines, detailed knowledge of the micromilieu in cancer lesions is warranted. In this study, flow cytometry and human transcriptome arrays were used to characterize subsets of DCs in head and neck squamous cell tonsillar cancer and compare them to their counterparts in benign tonsils to evaluate subset-selective biomarkers associated with tonsillar cancer. We describe, for the first time, four subsets of DCs in tonsillar cancer: CD123+ plasmacytoid DCs (pDC), CD1c+, CD141+, and CD1c-CD141- myeloid DCs (mDC). An increased frequency of DCs and an elevated mDC/pDC ratio were shown in malignant compared to benign tonsillar tissue. The microarray data demonstrates characteristics specific for tonsil cancer DC subsets, including expression of immunosuppressive molecules and lower expression levels of genes involved in development of effector immune responses in DCs in malignant tonsillar tissue, compared to their counterparts in benign tonsillar tissue. Finally, we present target candidates selectively expressed by different DC subsets in malignant tonsils and confirm expression of CD206/MRC1 and CD207/Langerin on CD1c+ DCs at protein level. This study descibes DC characteristics in the context of head and neck cancer and add valuable steps towards future DC-based therapies against tonsillar cancer.
|
|
| 3. |
- Ahlström-Emanuelsson, Cecilia, et al.
(författare)
-
Effects of topical formoterol alone and in combination with budesonide in a pollen season model of allergic rhinitis.
- 2007
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 101:6, s. 1106-1112
-
Tidskriftsartikel (refereegranskat)abstract
- Background: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma exudation effects. White available data suggest no or only marginal effects of beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether these drugs may add to the efficacy of anti-rhinitis drugs. Objective: To examine effects of a beta(2)-agonist, alone and in combination with an intranasal glucocorticosteroid, on symptoms and signs of allergic rhinitis. Methods: Patients were examined in a pollen season model. Budesonide 64 mu g, alone and in combination with formoterot 9 mu g, as well as formoterot 9 mu g alone was given in a placebo-controlled and crossover design. After 7 days of treatment, the patients received allergen challenges for 7 days. Symptoms and nasal peak inspiratory flow (PIF) were recorded. Nasal lavages with and without histamine were carried out at the end of each challenge series. These lavages were analysed for tryptase, eosinophil cationic protein (ECP), and alpha(2)-macroglobutin as indices of mast cell activity, eosinophil activity, and plasma exudation, respectively. Results: Budesonide reduced symptoms of allergic rhinitis and improved nasal PIF in the morning, in the evening as well as post allergen challenge. Formoterol alone did not affect symptoms or nasal PIF and did not affect the efficacy of budesonide. Tryptase, ECP, and alpha(2)-macroglobutin were significantly reduced by budesonide. Formoterol alone did not affect these indices and did not affect the anti-inflammatory effect of budesonide. Conclusion: The present dose of formoterot does not affect symptoms and inflammatory signs of allergic rhinitis and does not add to the efficacy of topical budesonide.
|
|
| 4. |
|
|
| 5. |
- Ahlström-Emanuelsson, Cecilia, et al.
(författare)
-
Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid
- 2002
-
Ingår i: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 89:2, s. 159-165
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. Objective: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. Methods: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 kg, budesonide 256 mug, and mometasone furoate 200 mug in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. Results: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 mug produced greater improvement than mometasone furoate 200 mug for nasal PIF 10 minutes after allergen-challenge (P < 0.05). Conclusion: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Alenmyr, Lisa, et al.
(författare)
-
Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis.
- 2012
-
Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 110, s. 264-268
-
Tidskriftsartikel (refereegranskat)abstract
- Transient receptor potential vanilloid-1 (TRPV1) has been implicated as a mediator of itch in allergic rhinitis. To address this possibility, we synthesized a TRPV1 blocker (SB-705498) for nasal administration in patients with seasonal allergic rhinitis. The pharmacological activity of SB-705498 was confirmed on human TRPV1-expressing HEK293 cells, using fluorometric calcium imaging, and in patients with allergic rhinitis subjected to nasal capsaicin challenges. The effect of SB-705498 was studied in patients with seasonal allergic rhinitis subjected to daily allergen challenges for seven days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 10 min. before each allergen challenge. Primary end-point was total nasal symptom score on days 5 to 7. Nasal peak inspiratory flow and eosinophil cationic protein content in nasal lavages were also monitored. Daily topical applications of SB-705498 at a concentration that inhibited capsaicin-induced nasal symptoms had no effect on total symptom score, nasal peak inspiratory flow and eosinophil cationic protein levels in allergen-challenged patients with seasonal allergic rhinitis. The individual symptom nasal itch or sneezes was also not affected. These findings may indicate that TRPV1 is not a key mediator of the symptoms in allergic rhinitis. However, additional studies, using drug formulations with a prolonged duration of action, should be conducted before TRPV1 is ruled out as a drug target in allergic rhinitis.
|
|
| 9. |
- Alenmyr, Lisa, et al.
(författare)
-
TRPV1-mediated itch in seasonal allergic rhinitis.
- 2009
-
Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64, s. 807-810
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with allergic rhinitis may be abnormally sensitive to stimulation of the ion channel transient receptor potential vanilloid-1 (TRPV1). Aim of the study: To examine effects of various TRP ion channel activators on sensory symptoms in allergic rhinitis prior to and during seasonal allergen exposure. Methods: Nasal challenges were carried out with the TRPV1-activators capsaicin, anandamide and olvanil. Moreover, challenges were performed with mustard oil (allylisothiocyanate) and cinnamaldehyde as well as menthol, activators of TRPA1 and TRPM8, respectively. Nasal symptoms were monitored after each challenge and compared with symptoms reported following corresponding sham challenges. Symptoms recorded after challenge prior to pollen season were also compared with challenge-induced symptoms during pollen season. Results: The TRPV1, TRPA1 and TRPM8-activators produced sensory symptoms dominated by pain and smart. During seasonal allergen exposure, but not prior to season, TRPV1-activators also induced itch. Furthermore, the seasonal challenge to the TRPV1-activator olvanil was associated with rhinorrhoea. Conclusion: Patients with allergic rhinitis feature an increased itch response to TRPV1 stimulation at seasonal allergen exposure. We suggest that this reflects part of the hyperresponsiveness that characterizes on-going allergic rhinitis. Intervention with the TRPV1-signalling pathway may offer potential treatments of this condition.
|
|
| 10. |
- Alenmyr, Lisa, et al.
(författare)
-
TRPV4-mediated calcium influx and ciliary activity in human native airway epithelial cells.
- 2014
-
Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 114:2, s. 210-216
-
Tidskriftsartikel (refereegranskat)abstract
- The transient receptor potential, vanilloid 4 (TRPV4), is a calcium permeable ion channel expressed in airway epithelial cells. Based on studies of cell lines and animals, TRPV4 has been suggested to play a role in the regulation of ciliary beat frequency (CBF). Whether the same is true for human ciliated epithelial cells is not known. Therefore, the aim was to examine the expression and function of TRPV4 in human native nasal epithelial cells. Expression of TRPV4 mRNA in nasal epithelial cells and in the cell lines BEAS2B and 16HBE was confirmed by quantitative real-time PCR. A marked apical TRPV4 immunoreactivity was observed in nasal epithelial cells using immunocytochemistry. Responses to pharmacological modulation of TRPV4 were assessed with calcium imaging and CBF measurements. The TRPV4 agonist GSK1016790A produced concentration-dependent calcium responses in TRPV4-expressing HEK293, BEAS2B and 16HBE cells, and the TRPV4 antagonist HC067047 caused a rightward shift of the GSK1016790A concentration-response curves. Nasal epithelial cells responded to the TRPV4 agonist GSK1016790A with increased intracellular calcium signals and increased CBF, followed by cessation of ciliary beating and cell death. These effects were prevented or inhibited by the TRPV4 antagonist HC067047, the TRP channel blocker ruthenium red or removal of extracellular calcium. We conclude that TRPV4 is expressed in human primary nasal epithelial cells and modulates epithelial calcium levels and CBF. Thus, TRPV4 may participate in mucociliary clearance and airway protection. However, exaggerated activation of TRPV4 may result in epithelial cell death. This article is protected by copyright. All rights reserved.
|
|
| 11. |
- Altunbulakli, Can, et al.
(författare)
-
Targeted spatial proteomic analysis of CD8+ T- and myeloid cells in tonsillar cancer
- 2023
-
Ingår i: Frontiers in Oncology. - 2234-943X. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Tonsillar cancer is caused by high-risk human papillomavirus (HPV), tobacco smoking, and alcohol abuse. Aspects of the patient’s immune response to this disease have arisen as prognostic factors and treatment targets, reflecting differences in the type and protein expression profile of immune cells. Because tonsillar cancers are heterogenous lesions such data need to be spatially resolved. Methods: In this study, we aim to explore inter-patient and intra-tumoral sources of variation in tonsillar cancer using immunofluorescence and targeted spatial proteomics to interrogate a cohort of 105 patients. Furthermore, we assess prognostic factors and elucidate molecular targets. We have used CD8, CD11c, and Pan-cytokeratin (PanCK) to quantify and locate immune cells driving antigen-specific cellular immunity. Guided by immunofluorescence information, we selected 355 CD8+, CD11c+, or PanCK+ areas inside and outside (i.e., stroma) cancer-cell islets, to quantify 43 immune-related proteins using digital spatial profiling. Results: Quantitative analysis of immunofluorescence in combination with clinical data revealed that the abundance of total CD8+ cells and CD8+ cells infiltrating cancer-cell islets, respectively, were associated with higher 5-year disease-free survival and overall survival, independently of HPV-status and clinical stage. Comparison of CD8+ cells inside and outside cancer-cell islets revealed an upregulation of effector CD8+ T-cell and immune checkpoint molecules in the former. Among these, the expression of PD-L1 by CD8+ T-cells was associated with lower all-cause mortality in a univariate proportional hazards model. Similarly, a comparison of tumor boundary and stroma CD11c+ cells showed upregulation of both co-stimulatory and immune checkpoint molecules with proximity to tumor cell islets. Conclusion: Our findings highlight the relevance of analyzing aspects of tumor micro-architecture in the search of prognostic markers and molecular targets for tonsillar cancer. The abundance of intra-tumoral CD8+ T-cells can be considered a positive predictive marker for tonsillar cancer, while the significance of PD-L1 expression by intra-tumoral CD8+ T-cells warrants further evaluation. Location-based differences in CD8+ and CD11c+ cells suggest an immune cell-altering effect on the tumor microenvironment, and grant new insight into which cells that can be targeted by novel therapeutic agents.
|
|
| 12. |
- Andersson, Morgan, et al.
(författare)
-
Barrier-enforcing measures as treatment principle in allergic rhinitis: a systematic review
- 2014
-
Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 30:6, s. 1131-1137
-
Forskningsöversikt (refereegranskat)abstract
- Background and objectives Barrier-enforcing measures have been suggested as treatment options for allergic rhinitis. This review identifies and describes the literature on the subject. Methods Relevant publications were searched for in the PubMed database (search entries: 'allergic rhinitis' and 'treatment'). The evaluation comprised condition (seasonal or perennial allergic rhinitis), type of intervention, duration of treatment, study design, peer review status or not, number of test subjects, type of allergen exposure, and outcome in terms of effects or not on nasal symptoms of allergic rhinitis. Results Fifteen studies were either identified in the PubMed database search or from the reference lists of identified publications. Seven were placebo-controlled, randomized, and peer-reviewed, and symptom-reducing effects were reported by all of these reports. Limitations of this review reflect that the remainder of the studies had inferior designs, particularly lack of placebo control. Conclusions Barrier-enforcing measures as achieved by nasal administrations of cellulose powder and microemulsions, respectively, have symptom-reducing effects in allergic rhinitis.
|
|
| 13. |
- Andersson, Morgan, et al.
(författare)
-
Effects of a topical microemulsion in house dust mite allergic rhinitis.
- 2011
-
Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 108:2, s. 146-148
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously demonstrated that a topical microemulsion can attenuate symptoms and signs of seasonal allergic rhinitis. This likely reflects that the microemulsion interferes with the interaction between the allergen and the mucosa. Whether or not the finding translates to conditions caused by other inhaled agents such as house dust mite allergen is unknown. Patients with perennial allergic rhinitis caused by house dust mite were subjected to topical microemulsion treatment in a randomized, double-blinded and crossover design with isotonic saline as control. Morning symptoms were monitored, change from baseline was assessed and the treatments were compared. On the first days of the isotonic saline and microemulsion runs, before any treatment was given, total nasal symptoms were scored to 2.8 and 3.1 (range 0-9), respectively. Nasal symptoms were reduced by intervention with the microemulsion: the change from baseline was consistent for the microemulsion and the difference between the microemulsion and isotonic saline reached statistical significance in favour of the former. We conclude that intervention with a microemulsion may reduce symptoms of house dust mite allergic rhinitis at natural allergen exposure. Our findings suggest the possibility that topical microemulsions can be a useful option to reduce nasal mucosal exposure to allergen in perennial allergic rhinitis..
|
|
| 14. |
|
|
| 15. |
- Andersson, Morgan, et al.
(författare)
-
Nasal treatment with a microemulsion reduces allergen challenge-induced symptoms and signs of allergic rhinitis
- 2008
-
Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 128:6, s. 666-669
-
Tidskriftsartikel (refereegranskat)abstract
- Conclusions. Intranasal microemulsion treatment can attenuate allergen challenge-induced nasal symptoms and plasma exudation in allergic rhinitis. We hypothesize that the mechanism of action involves modification of the allergen-mucosa interaction. The present observation suggests a novel principle for prevention in allergic rhinitis. Objective. To evaluate a specific microemulsion as a treatment for allergic rhinitis in an acute allergen challenge model. Patients and methods. Patients with allergic rhinitis were examined out of the pollen season. Treatment with a single dose of a specific microemulsion was given in a single-blind, placebo-controlled, and crossover design using a nasal pool device. Nasal allergen challenges were carried out and symptoms of allergic rhinitis were scored. Furthermore, nasal lavages were performed and levels of the plasma protein alpha(2)-macroglobulin were measured as an index of exudative inflammation. Results. The allergen challenges produced significant increases in nasal symptoms (p = 0.007) and in nasal lavage fluid levels of alpha(2)-macroglobulin (p = 0.008). The challenge-induced symptoms as well as the plasma exudation were attenuated by treatment with the microemulsion (p = 0.016 and 0.012, respectively, compared with placebo).
|
|
| 16. |
- Andersson, Morgan, et al.
(författare)
-
Wine produced by ecological methods produces relatively little nasal blockage in wine-sensitive subjects.
- 2009
-
Ingår i: Acta Oto-Laryngologica. - 1651-2251. ; 129:11, s. 1232-1236
-
Tidskriftsartikel (refereegranskat)abstract
- CONCLUSION: Subjects with self-reported nasal symptoms following consumption of red wine may respond with less nasal blockage to a wine produced with ecological methods than to wine not labelled as ecologically produced. OBJECTIVE: To compare nasal symptoms following intake of three different wines--one that was ecologically produced and two that were traditionally produced. SUBJECTS AND METHODS: Individuals with self-reported nasal symptoms following consumption of red wine were subjected to controlled intake of three different wines in a double-blinded, randomized, and crossover design. Nasal symptoms and peak nasal inspiratory flow (PNIF) were monitored before and 15, 30, 45, and 60 min following intake of wine. RESULTS: All wines produced nasal symptoms, notably nasal blockage. While blockage scores did not differ between the two non-ecological wines, the ecological wine was associated with significantly lower blockage scores, as compared with both the other wines.
|
|
| 17. |
- Andreasson, Ulrika, et al.
(författare)
-
The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution
- 2006
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 362:2, s. 212-227
-
Tidskriftsartikel (refereegranskat)abstract
- Upon encounter with antigen, the B lymphocyte population responds by producing a diverse set of antigen-specific antibodies of various isotypes. The vast size of the responding populations makes it very difficult to study clonal evolution and repertoire composition occurring during these processes in humans. Here, we have explored an approach utilizing the H-EPSILON-encoding transcriptome to investigate aspects of repertoire diversity during the season of antigen exposure. We show through sequencing of randomly picked transcripts that the sizes of patients' repertoires are relatively small. This specific aspect of the transcriptome allows us to construct evolutionary trees pinpointing features of somatic hypermutation as it occurs in humans. Despite the small size of the repertoires, they are highly diverse with respect to VDJ gene usage, suggesting that the H-EPSILON-encoding transcriptome is a faithful mimic of other class-switched isotypes. Importantly, it is possible to use antibody library and selection technologies to define the specificity of clonotypes identified by random sequencing. The small size of the H-EPSILON-encoding transcriptome of peripheral blood B cells, the simple identification of clonally related sets of genes in this population, and the power of library and selection technologies ensure that this approach will allow us to investigate antibody evolution in human B lymphocytes of known specificity. As H-EPSILON repertoires show many of the hallmarks of repertoires encoding other isotypes, we suggest that studies of this type will have an impact on our understanding of human antibody evolution even beyond that occurring in the IgE-producing B cell population.
|
|
| 18. |
- Askmyr, David, et al.
(författare)
-
Pattern recognition receptor expression and maturation profile of dendritic cell subtypes in human tonsils and lymph nodes
- 2021
-
Ingår i: Human Immunology. - : Elsevier BV. - 0198-8859. ; 82:12, s. 976-981
-
Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) with capacity of antigen cross-presentation are of key interest for immunotherapy against cancer as they can induce antigen-specific cytotoxic T lymphocyte (CTL) responses. This study describes frequencies of DC subtypes in human tonsils and lymph nodes, and phenotypic aspects that may be targeted by adjuvant measures. From human tonsils and neck lymph nodes, DCs were identified through flow cytometry, and subsets of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were investigated. Maturity status was assessed and surface receptors with CTL-promoting potentials were studied. CD123+ pDCs as well as CD1c+, CD141+, and CD1c-CD141- mDCs were detected in tonsils and lymph nodes. Both sites featured a similar presence of DC subsets, with CD123+ pDC being dominant and CD141+ mDCs least frequent. Based on CD80/CD86 expression, all DC subtypes featured a low degree of maturation. Expression of pattern recognition receptors (PRRs) CD206, CD207, DC-SIGN, TLR2, and TLR4, as well as the chemokine receptor XCR1, indicated DC subset-specific receptor profiles. We conclude that tonsils and lymph nodes share common features in terms of DC subset frequency and maturation as well as PRR and XCR1 expression pattern. Our work suggests that both sites may be considered for vaccine deposition in DC-mediated immunotherapy.
|
|
| 19. |
|
|
| 20. |
- Broos, Sissela, et al.
(författare)
-
Immunomodulatory nanoparticles as adjuvants and allergen-delivery system to human dendritic cells: Implications for specific immunotherapy.
- 2010
-
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28, s. 5075-5085
-
Tidskriftsartikel (refereegranskat)abstract
- Novel adjuvants and antigen-delivery systems with immunomodulatory properties that shift the allergenic Th2 response towards a Th1 or regulatory T cell response are desired for allergen-specific immunotherapy. This study demonstrates that 200-nm sized biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) are activators of human monocyte-derived dendritic cells (MoDCs). gamma-PGA NPs are efficiently internalized by immature MoDCs and strongly stimulate production of chemokines and inflammatory cytokines as well as up-regulation of co-stimulatory molecules and immunomodulatory mediators involved in efficient T cell priming. Furthermore, MoDCs from allergic subjects stimulated in vitro with a mixture of gamma-PGA NPs and extract of grass pollen allergen Phleum pratense (Phl p) augment allergen-specific IL-10 production and proliferation of autologous CD4(+) memory T cells. Thus, gamma-PGA NPs are promising as sophisticated adjuvants and allergen-delivery systems in allergen-specific immunotherapy.
|
|
| 21. |
- Cervin, Anders, et al.
(författare)
-
Acute exudative inflammation and nasally exhaled nitric oxide are two independent phenomena
- 2002
-
Ingår i: ORL. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 64:1, s. 26-31
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Increased levels of nitric oxide (NO) and the exudations of plasma proteins to the airway lumen have both been considered characteristics of airway inflammation. The aim of the present study was to investigate a possible relationship between nasal NO concentrations and acutely induced exudative inflammation of the nasal mucosa. Methods: Twelve healthy non-allergic subjects participated. Nasal challenges with saline, histamine 40 mug/ml (M), histamine 400 mug/ml (H2), oxymethazoline, 0.25 mg/ml (OXY), and a combination of oxymethazoline 0.25 mg/ml and histamine 800 mug/ml (OXYH), were performed on separate occasions. Exhaled NO was measured after each challenge, and alpha(2)-macroglobulin (as a marker of plasma exudation) was measured in nasal lavage fluids after the H 1 and H2 challenges. Results: The mean baseline NO in all measurements was 164 +/- 10.3 ppb. Saline and H1 challenge did not change NO and a2-macroglobulin levels. H2 challenge showed a tendency to reduce NO levels, and the most pronounced decrease was seen after 10 min (-36.3 +/- 16.3%, p = 0.07). This reduction was sustained throughout the registration period. Simultanousley with the decrease in NO, alpha(2)-macroglobulin levels were increased significantly. OXY challenge alone reduced NO significantly throughout the whole registration period. Maximum decrease was seen at 40 min (-21.3 +/- 3.4%, p = 0.03). The OXYH challenge also reduced NO, with a maximal reduction recorded at 10 min (-29.4 +/- 6.4%, p = 0.03). The reduction of NO was sustained throughout the registration period (p < 0.01). Conclusion: Histamine 400 mug/ml induced a prompt plasma exudation response whereas a decrease in nasal NO was registered, suggesting that these two events are not necessarily linked. Furthermore it was shown that the vasoconstrictor oxymethazoline reduced nasal NO, which could be related to reduced mucosal blood flow, whereas the reduction of nasal NO after histamine challenge remains to be elucidated. Copyright (C) 2002 S. Karger AG, Basel.
|
|
| 22. |
- Cervin, Anders, et al.
(författare)
-
Effects of long-term clarithromycin treatment on lavage-fluid markers of inflammation in chronic rhinosinusitis
- 2009
-
Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 29:2, s. 136-142
-
Tidskriftsartikel (refereegranskat)abstract
- Macrolides can be clinically effective in chronic rhinosinusitis (CRS). However, little is known about how these drugs affect pathophysiological features of CRS in vivo. In the present study, patients with CRS were subjected to long-term treatment with clarithromycin. Nasal lavages with and without histamine (40 and 400 mu g ml(-1)) were carried out prior to and late into the treatment period. Histamine was included as a tool to produce plasma exudation, a process known to move free cellular products from the mucosal tissue into the airway lumen thereby enriching nasal surface liquids with such products. Interleukin-8 (IL-8), myeloperoxidase (MPO), eosinophil cationic protein (ECP), alpha(2)-macroglobulin and fucose were monitored as indices of pro-inflammatory cytokine production, neutrophil and eosinophil granulocyte activities, plasma exudation and mucinous secretion, respectively. Clarithromycin reduced the lavage fluid levels of IL-8 at the low-dose histamine observation (P < 0.001). There was a trend towards reduced MPO by the treatment, whereas ECP was significantly reduced at the low-dose histamine observation (P < 0.05). alpha(2)-Macroglobulin was reduced by clarithromycin (saline lavages) (P = 0.05), whereas fucose was unaffected. The exudative responsiveness to high-dose histamine was significantly reduced by the treatment (P < 0.05). Furthermore, significantly lower levels of fucose were observed at the low-dose histamine observation (P < 0.01). We conclude that long-term clarithromycin treatment likely exerts an anti-inflammatory effect in CRS.
|
|
| 23. |
- Cervin, Anders, et al.
(författare)
-
Nasal Septal Perforations during Treatment with Topical Nasal Glucocorticosteroids Are Generally Not Associated with Contact Allergy to Steroids.
- 2003
-
Ingår i: ORL. - : S. Karger AG. - 0301-1569 .- 1423-0275. ; 65:2, s. 103-105
-
Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Mucosal ulcers and perforations of the nasal septum are very rare and may have several underlying causes. Contact allergy to steroids has been suggested as a possible aetiological factor in patients who develop perforations during topical steroid use. <i>Methods:</i> We have identified 13 subjects with perforations of their nasal septum and concomitant topical nasal steroid use. In order to evaluate whether these patients had developed contact allergy to steroids they underwent patch testing with an extended steroid series. <i>Results:</i> None of the subjects displayed any positive reaction to the steroids. <i>Conclusion:</i> Sensitivity to glucocorticoids is a well-described phenomenon and may in selected subjects also be associated with local side effects to nasal sprays. However, contact allergy to steroids does not seem to be a general explanation for septal perforations in patients using nasal steroids.
|
|
| 24. |
- Erjefält, Jonas, et al.
(författare)
-
Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways
- 1999
-
Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 160:1, s. 304-312
-
Tidskriftsartikel (refereegranskat)abstract
- Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of allergic airway diseases such as rhinitis and asthma. To explore the cellular mechanisms behind eosinophil granule release in human allergic airways, 16 symptom-free patients with seasonal allergic rhinitis were challenged daily with allergen during 1 wk. Nasal lavage samples and biopsies, obtained before and 24 h after the last allergen exposure, were processed for immunohistochemical and electron microscopic analysis. The allergen challenges produced nasal symptoms, marked tissue eosinophilia, and an increase in lavage fluid levels of eosinophil cationic protein (ECP). The nasal mucosa areas with intense extracellular immunoreactivity for ECP were associated with abundant free eosinophil granules. Electron microscopy confirmed the free granules and revealed that all mucosal eosinophils were involved in granule release, either by cytolysis (33%) or piecemeal degranulation (PMD) (67%). Resting or apoptotic eosinophils were not observed. Cytolytic eosinophils had less signs of intracellular granule release (p < 0. 001) and a higher content of intact granules (p < 0.001) compared with viable eosinophils in the same tissue. This study demonstrates eosinophil cytolysis (ECL) as a distinct mechanism for granule mediator release in human allergic airway mucosa. The nature and extent of the ECL and its product (i.e., protein-laden extracellular granules) indicate that allergen-induced cytolysis is a primary and major mechanism for the release of eosinophil proteins in human allergic airway inflammation in vivo.
|
|
| 25. |
- Erjefält, Jonas, et al.
(författare)
-
Cytolysis and piecemeal degranulation as distinct modes of activation of airway mucosal eosinophils
- 1998
-
Ingår i: Journal of Allergy and Clinical Immunology. - 1097-6825. ; 102:2, s. 286-294
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of inflammatory airway diseases, including asthma, rhinitis, and polyposis. However, little is known about the mechanisms involved in the deposition of these tissue-damaging granular products in vivo. OBJECTIVE: We sought to determine the occurrence of degranulating eosinophils, those with morphologic evidence of cytolysis with associated clusters of free eosinophil granules (Cfegs), and to identify the frequency of apoptotic eosinophils in inflamed upper airway tissue. METHODS: Eosinophil-rich nasal polyps were processed for transmission electron microscopy and for light microscopic evaluation of whole-mount preparations subjected to deep tissue staining for eosinophil peroxidase. RESULTS: The mean proportion of eosinophil subtypes were intact and resting (6.8%), intact but degranulating (83%), cytolytic or Cfegs (9.9%), and apoptotic (0.0%). All degranulating eosinophils exhibited piecemeal degranulation. The occurrence of Cfegs was confirmed in nonsectioned whole-mount preparations. Depending on the appearance of their core and matrix, the specific granules were divided into four subtypes, and a degranulation index (altered per total granules) was calculated for each eosinophil. Cytolytic eosinophils had a much lower degranulation index than intact eosinophils present in the same tissue (P < .001). CONCLUSIONS: These data indicate that eosinophil cytolysis is present in human airway mucosa, that its occurrence is not an artifact of the means of tissue handling, and that cytolysis of eosinophils may occur without prior extensive degranulation. We suggest that eosinophil cytolysis is a major activation mechanism, which occurs along with, but is distinct from, other types of degranulation.
|
|
