bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigen presenting cells in the nasal mucosa of patients with allergic rhinitis during allergen provocation
Authors: GODTHELP T. , FOKKENS W. J. , KLEINJAN A. , HOLM A. F. , MULDER P. G. H. , PRENS E. P. , RIJNTES E. 
Published: April 2006

SummaryBackground
The role of antigen presenting cells (APC) in allergic rhinitis is underexposed. Allergen presentation to T lymphocytes is probably an important aspect of the pathophysiological mechanism of allergic rhinitis.Objectives
The aim of the study was to investigate the presence and dynamics of APC with special emphasis on Langcrhans cells (LC) in the nasal mucosa of patients with an isolated grass pollen allergy during an out‐of‐season 2‐week allergen exposure, mimicking the natural grass pollen season.Methods
Seventeen patients with isolated grass pollen allergy and four control subjects were challenged daily with allergen during a 2‐week period in the winter. Biopsy specimens were obtained once before, six times during and once after the provocation period. Biopsy sections were stained with monoclonal antibodies: OKT6 (CDla‐Langerhans cells). Ki‐M6 (CD68 macrophages), L25 (dendritic cells), anti‐IgE, HLA‐DR and HLA‐DQ (Major Histoeompatibihty Complex Class II ‐ antigen presenting eells), as well as staining with acid phosphatase.Results
APC with different characteristics are present in the epithelium and lamina propria of the nasal mucosa. The number of LC increased significantly in epithelium and lamina propria. IgE+‐LC were present in the nasal mucosa and increase during provocation, HLA‐DR+ cells with dendritic and lymphocytic morphology and HLA‐DQ+ cells were found. The number of these cells increased during provocation in epithelium and lamina propria. The number of HLA‐DR+ epithelial cells did not change. A significant increase in the number of Ki‐M6+ cells (macrophages) was found in the lamina propria. However, Ki‐M6+ cells increased to the same extent in the lamina propria in the control group.Conclusion
APC are influenced by allergen provocation. This study supports the hypothesis that (IgE+) LC are involved in allergic rhinitis. The role macrophages play remains doubtful.
IL‐4 induced leucocyte trafficking in cynomolgus monkeys: correlation with expression of adhesion molecules and chemokine generation
Authors: GUNDEL R. , LINDELL D. , HARRIS P. , FOURNEL M. , JESMOK G. , GERRITSEN M. E. 
Published: April 2006

SummaryBackground
Interleukin‐4 (IL‐4) is an immunoregulatory cytokine which has a wide variety of effects on immune cell function. In addition, recent studies suggest that IL‐4 may have effects on other cells including endothelial cells in terms of the regulation of adhesion molecule expression and leucocyte extravasation from the vascular space to sites of tissue inflammation. Consequently, IL‐4 may have an important role in the pathogenesis of allergic inflammation and disease.Objective
The purpose of this study was to learn more about the potential role of IL‐4 in inflammatory disease, specifically in regard to the potential of IL‐4 to induce the expression of adhesion molecules on vascular endothelial cells and promote the adherence and transmigration of circulating leucocytes to sites of tissue inflammation.Methods
Single subcutaneous injections of human IL‐4 were administered to cynomolgus monkeys and tissue biopsy samples were obtained and analysed for adhesion molecule expression on vascular endothehum and inflammatory cell infiltrates. In another series of experiments, multiple subcutaneous injections of human IL‐4 were administered (bid on four consecutive days) and the effects on peripheral blood leucocytes and plasma levels of various cytokines and chemokines were examined. Results Intradermal injection of IL‐4 induced the expression of vascular cell adhesion molecule‐1 (VCAM‐l) on cutaneous vascular endothelium that was present at 8hr and persisted out to 24h post injection. The expression of VCAM‐1 was associated with an inflammatory cell infiltrate comprised of granulocytes and mononuclear cells. Multiple injections of IL‐4 resulted in a dose‐related decrease in the relative percentage and total number of circulating lymphocytes and an increase in circulating neutrophils (4.6 ± 1–2.1 ± 0.2 ± 106/mL and 1.7 ± 0.3–7.0 ± 1 ± 106/mL, respectively). Analysis of cell surface markers by flow cytometry revealed a transient decrease in the number of CD4+ T lymphocytes and a sustained decrease in CD16+ cells. In addition. IL‐4 administration resulted in a large increase in plasma MCP‐1 concentration.Conclusion
This is the first study to demonstrate an acute eflect of IL‐4 consistent with lymphocyte trafficking out of the vascular space, the induction of VCAM‐l expression on vascular endothelium and increases in plasma levels of MCP‐1 in vivo. We suggest that IL‐4 may be involved in the early recruitment of mononuclear cells to sites of tissue inflammation by the upregulation of VCAM‐l expression on vascular endothelium and the generation and release of potent chemoattractants.
Analysis of sequence polymorphism of a major mite allergen, Der p 2
Authors: CHUA K.Y. , HUANG CH. , SHEN H.D. , THOMAS W.R. 
Published: April 2006

SummaryBackground
The major house dust mite allergen Der p 2 has been regarded as an important allergen involved in the immunopathogenesis of allergic asthma and eczema. Objectives To determine the degree of sequence polymorphism exists in Der p 2 at both the genomic DNA and cDNA levels.Methods
Isolation of cDNA clones was performed by screening the cDNA libraries with Der p 2 cDNA probe and the genomic sequences for Der p 2 were obtained by PCR amplification from environmental dust mites with Der p 2‐specific primers. DNA sequencing was carried out by the dideoxynucleotide chain termination method. The study of Der p 2 isoforms was performed by 2‐D gel immunoblot analysis using mouse anti‐Der p 2 serum.Results
In this study, we have characterized the seqtiences of three difierent genealleles coding for the major house dust mite allergen Der p 2 at the cDNA level. The translated polypeptides from these clones differed from each other by 3–4 amino‐acid residues. These polymorphic residues determined were also found in Der f 2 and they were located in regions containing T‐epitopes. In addition, the genomic DNA sequences of Der p 2 which were obtained by PCR amplification using the environmental mites isolated from Taiwan and Australia have helped to confirm the authenticity of the polymorphisms detected in the cDNA clones generated from CSL cultured mites. Furthermore, 2D‐ immunoblot analysis indicated that there were at least 10 different isoforms (p 1 values range from greater than 7.0–5.9) of Der p 2 proteins produced by CSL cultured mites.Conclusion
The results showed that there was a small but significant degree of sequence polymorphisms exists in Der p 2 gene alleles. Interestingly, the polymorphic residues were found in regions containing previously determined T‐epitopes. The polymorphism data reported here will be important for the understanding of the immune responses of mite allergens as well as for the development of the peptide‐based immunotherapeutic reagents for mite allergy.
Relationship between nasal hyperreactivity, mediators and eosinophils in patients with perennial allergic rhinitis and controls
Authors: DE GRAAF‐INT VELD C. , GARRELDS I. M. , KOENDERS S. , GERTH VAN WIJK R. 
Published: April 2006

SummaryBackground
In perennial allergic rhinitis, patients are almost daily exposed to aeroallergens. This ongoing allergic reaction results in increased sensitivity to allergens and non‐specific stimuli. It is generally known that inflammatory cells and mediators are involved in the pathogenesis of the allergic reaction.Objectives
To study the relationship between nasal hyperreactivity and nasal inflammation during natural allergen exposure.Methods
In 48 patients with perennial allergic rhinitis and in 11 volunteers a nasal brush, a nasal lavage and a histamine challenge were performed. Nasal inflammation was estimated by the number of eosinophils, levels of albumin, tryptase, prostaglandin D2 (PGD2), eosinophil cationic protein (ECP) and leukotriene C4/D4/E4 (LTC4/D4/E4).Results
In contrast to PGD2 and tryptase, eosinophils (1.9 vs 0%, P = 0.0023), LTC4/ D4/E4 (17.51 vs 1.43pg/mL, P= 0.0001) and albumin (8.61 vs 2.37mg/mL, P= 0.0008) were significantly increased in rhinitis patients as compared with controls. Patients also showed increased responses to nasal histamine challenge assessed using a composite symptom score (21.5 vs 4 points, P=0.0001). The nasal response to histamine was weakly correlated with the total number of eosinophils in the cytospin (correlation coefficient r=0.38, P= 0.009).Conclusion
Nasal hyperreactivity is correlated with the percentage of eosinophils in patients with perennial rhinitis. The patients' mediator profiles suggest that eosinophils are important in the ongoing allergic reaction and nasal hyperreactivity.
Reduction in humidity as a method of controlling mites and mite allergens: the use of mechanical ventilation in British domestic dwellings
Authors: FLETCHER A. M. , PICKERING C. A. C. , CUSTOVIC A. , SIMPSON J. , KENNAUGH J. , WOODCOCK A. 
Published: April 2006

SummaryBackground
Low humidity is an important limiting factor for mite population growth. Reducing humidity can therefore be used as a method to control mites within the home.Objective
Ihis study investigated the effect of mechanical ventilation heat recovery (MVHR) units on house dust mites and mite allergen Der p I in typical homes in the North‐West of England.Methods
Mite counts and Der p 1 levels were measured at 3‐monthly intervals over a period of 1 year in 18 houses (nine with MVHR units and nine architecturally matched control houses). Paired dust samples were collected using a vacuum cleaner with an air‐flow rate 451/sec, adapted to collect the sample onto a preweighed filter paper. A 1 m2 area of bedroom carpet, living room carpet and mattress was sampled for 2min. Indoor temperature and relative humidity (RH) levels were recorded for a period of 1 week before and after the winter period (November and February: 3 and 6 months data sets). The environmental questionnaire was completed at the beginning and at the end of the study.Results
No difference in either Der p 1 concentrations or mite counts in any of the sampling sites at 3, 6, 9 and 12 months as compared with the baseline values was found, both within and between the groups (P > 0.1). The measured levels of RH performed in autumn and winter were found to be lower in the MVHR houses compared to the architectural controls. The indoor temperature during each period did not differ between the groups. Questionnaire data showed that the severity of condensation improved in the MVHR homes, whilst during the winter period, the severity of condensation had increased in the architectural control group.Conclusions
The MVHR unit does not reduce indoor humidity to levels capable of retarding mite population growth and decreasing mile allergens in the type of houses predominantly found in the mild and humid climate of the North‐West of England.
The rationale for use of topical corticosteroids in allergic rhinitis
Authors: MYGIND N. , DAHL R. 
Published: April 2006

SummaryThe rationale for using topical corticosteroids in the treatment of allergic rhinitis is that high drug concentrations can be achieved at receptor sites in the nasal mucosa, with minimal risk of systemic adverse effects. Topical corticosteroids have been demonstrated to reduce the number of Langerhans' cells (or their markers) in the nasal mucosa, and this is thought to attenuate antigen presentation. T lymphocytes have been identified as being significant in orchestrating the immune‐inflammatory response, particularly the TH2 cells, which represent an important target for topical corticosteroids. TH2 cell‐evoked mast cells and basophils are the sole producers of histamine, a mediator of major importance for rhinitis symptoms. Several studies have shown that the increased number of mast cells and basophils in the epithelium following antigen challenge/exposure, are markedly reduced by topical corticosteroids. Furthermore, the number of eosinophils, an important morphological marker of allergic rhinitis, can be profoundly reduced by treatment with topical corticosteroids. The rationale for topical treatment is strengthened by evidence of inhibition of cytokine release from surface epithelial cells, resulting in reduced recruitment and activation of mast cells, basophils, and eosinophils, which may be attributed to the high drug concentration achieved in epithelial cells. Ongoing inflammation in the mucous membrane is indicated by entry of plasma into the nasal lumen which subsides with the anti‐inflammatory efficacy of topical corticosteroids. In contrast to anlihistamine therapy, which has little effect on nasal blockage, pretreatment with topical corticosteroids results in almost complete attenuation of late‐phase symptoms including nasal blockage, and moderate efficacy in early phase symptoms. Clearly, the spectrum of anti‐inflammatory activity afforded by topical corticosteroid therapy is of clinical significance in reducing the three major symptoms of allergic rhinitis — sneezing, watery rhinorrhoea and nasal blockage.
Challenge tests in nose and bronchi: pharmacological modulation of rhinitis and asthma
Authors: MYGIND N. , DAHL R. 
Published: April 2006

SummaryIn order to study the pathophysiology of allergic airway disease and its response to pharmacotherapy, allergic and non‐allergic provocation challenge techniques can be employed. Lower airway challenge has been used widely, but the use of nasal challenge is becoming more widespread as its advantages are realized. New measurement techniques are also being used (e.g. acoustic rhinometry), along with more classical methods such as spirometry, peak airflow rate and symptom scores, to determine the response to challenge. In the lungs, allergen challenge produces a biphasic response, which is less clearly defined in the nose. Topical histamine challenge closely resembles the effects of an allergic reaction and acts by stimulating sensory nerve endings. Methacholine is also often used for nasal challenge (often in addition to histamine), due to its effects on glandular sensitivity. Exercise induces bronchoconstriction in asthmatics and can be imitated by inhalation of cold, dry air. Cold air induces glandular hypersecretion and nasal discharge in normal subjects, which is increased in severity in rhinitic patients. Drug effect investigations using antihistamines have shown that histamine is important in producing the symptom of sneezing, whereas nasal blockage is due to vasodilatation rather than plasma exudation and oedema. β2‐agonists reduce allergen‐induced symptoms by stabilizing mast cells, whereas cholinoceptor antagonists reduce watery nasal secretion. Increased responsiveness of sensory nerves and nasal glands is a characteristic clinical feature of asthma and rhinitis, which is responsible for the symptomatology. These effects can be reduced by topical corticosteroids.
Pathology of rhinitis and bronchial asthma
Authors: DJUKANOVIC R. , WILSON S. J. , HOWARTH P. H. 
Published: April 2006

SummaryStudies of the pathology of rhinitis and asthma have identified similarities and differences between these two clinical conditions. With regard to symptoms, both the nose and the lower airways respond to neural stimulation by irritant substances, but a major difference is that engorgement of the capacitance vessels is the main cause of nasal obstruction in rhinitis, while muscle constriction is the major determinant of lower airway narrowing. There are also similarities and differences with respect to the role of infiammatory cells. In both conditions there is evidence of allergen‐induced mast cell activation, with production of an array of mediators (some mast cell‐derived and others originating from a variety of other cell types). Eosinophilia is also characteristic of both diseases — it is prominent even in mild forms of asthma, but is low in pollen‐sensitive rhinitics outside of the season. T‐cell activation and production of cytokines plays an important role in the development and maintenance of allergic disease, but the level of T‐cell activation may differ between asthma and rhinitis. Further research into differences in cellular activity and response to treatment between these two diseases may help define factors which will determine whether atopic disease is expressed in the upper, lower, or both parts of the respiratory tract.
Azelastine eye drops reduce and prevent allergic conjunctival reaction and exert anti‐allergic activity
Authors: CIPRANDI G. , BUSCAGLIA S. , CATRULLO A. , PESCE G. , FIORINO N. , MONTAGNA P. , BAGNASCO M. , CANONICA G. W. 
Published: April 2006

SummaryBackground Azelastine is a selective H1‐receptor antagonist, which has previously been demonstrated to be effective in the treatment of allergic rhinitis. We have recently demonstrated that nasal azelastine inhibits the clinical and intlammatory events following nasal allergen challenge. Particularly, we focused our attention on ICAM‐1 expression on epithelial cells, since it is the natural ligand of LFA‐1, an adhesion molecule expressed by leucocytes, including eosinophils.Objective Since azelastine ocular drops are now available, the aim of the present study was the evaluation of the anti‐allergic activity in the model of allergen specific conjunctival challenge (ASCC).Methods Twenty outpatients with allergic rhinoconjunctivitis due to Parietaria Judaica (Wall Parietary) were included outside the pollen season. The study was designed as randomized, placebo‐controlled, double‐blind and parallel group, developed in two parts. The fonner investigated the onset of effect of a single dose of azelastine eye drops administered 20min after clinical response due to ASCC. The latter evaluated the clinical and inflammatory parameters following ASCC after 7‐days treatment with azelastine. Clinical parameters (hyperaemia, itching, lacrimation and eyelid swelling) were evaluated at baseline, 5, 10, 20 and 30 min (i.e. early phase reaction‐EPR) and 6h (i.e. late phase reaction‐LPR) after ASCC. Cytological assessment (number of neutrophils, eosinophils. monocytes and lymphocytes) and ICAM‐1 expression on conjunctival epithelial cells were evaluated at baseline, 30 min (i.e. early phase reaction‐EPR) and 6h (i.e. late phase reaction‐LPR) after ASCC.Results When administered 30 min after ASCC, azetastine produced a clinical effect ranging between 10 and 20 min after eye drops administration (P < 0.01). After 7 days of treatment, 30 min after ASCC, azelastine induced a reduction of symptom scores during EPR and LPR (P<0.01), a reduction of inflammatory cell infiltration during both EPR (P 0.01) and LPR (P 0.01), and a reduction of ICAM‐1 expression during EPR and LPR (both P 0.01). Placebo did not modify any of the studied parameters.Conclusion Azelastine eye drops exert anti‐allergic activity, inducing a rapid improvement of clinical events when administered after ASCC, and reducing both sytiiptoms and cellular infiltration when administered before ASCC. Finally, azelastine down‐regulates ICAM‐1 expression on epithelial conjunctival cells, confirming the results obtained at nasal level.
Heterogeneous proteolytic specificity and activity of the house dust mite proteinase allergen Der p I
Authors: HEWITT C. R. A. , HORTON H. , JONES R. M. , PRITCHARD D. I. 
Published: April 2006

SummaryBackground Exposure of the skin or respiratory tract to proteinases is frequently associated with allergic sensitization. This is of particular significance in the domestic indoor environment where the proteolytic activity of Der p I, the group I allergen of the house dust mite Dermatophagoides pteronyssinus, may influence the allergenicity of mites. Using class‐specific proteinase inhibitors and active‐site affinity chromatography, we have previously shown that Der p I exhibits a mixed cysteine‐serine proteinase activity. Measurement of the amount of cleavage, however, did not determine whether the inhibitors used were targeting exactly the same proteolytic mechanism.Objective To resolve this issue, we have examined whether the cleavage specificity of the cysteine and serine proteinase activities of Der p I was the same.Methods HPLC and mass spectrometry were used to analyse and identify the products of a Der p I‐digested peptide substrate and thus identify the peptide bonds cleaved.Results Der p I cleaves different peptide bonds, depending upon the class of proteolytic mechanism used. In the model peptide substrate insulin B chain, the cysteine and serine proteinase activities of Der p I showed preference for glutamic acid and arginine respectively in the P1 position.Conclusion These data suggest the existence of more than one mechanistic form of the allergen immunologically identified as Der p I. If proteolytic activity is indeed a function of allergenicity, this information may have important implications for the pathogenicity of Der p I and the ability of innate antiproteinase defences in the respiratory tract to prevent immune sensitization.
The effect of anti‐IL‐4 monoclonal antibody, rapamycin and interferon‐γ on airway hyperreactivity to acetylcholine in mice
Authors: NAGAI H. , MAEDA Y. , TANAKA H. 
Published: April 2006

SummaryBackground The role of IgE in airway hyperreaetivity is obscure.Objective In order to clarify the role of IgE in airway hyperreactivity, we investigated the effect of anti‐IL‐4 monoclonal antibody, rapamycin and interferon‐γ on the antigen‐induced IgE response, airway eosinophilia and hyperreactivity in mice.Methods Mice were immunized with an antigen (ovalbumin; OA) at intervals of 12 days. OA was inhaled 10 days after the secondary immunization. Twenty‐four hours after the last inhalation, airway reactivity to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was obtained.Results Three inhalations of antigen caused an increase in the number of eosinophils in bronchoalveolar lavage fluid (BALF) and in airway hyperreactivity to acetylcholine with a significant elevation of serum IgE level. Anti‐IL‐4 at a dose of 1000 μg/animal and rapamycin at doses between 0.1 and 1 mg/kg inhibited the IgE production, but did not affect the airway eosinophilia or hyperreactivity to acetylcholine. In contrast, IFN‐γ clearly inhibited the antigen‐induced airway eosinophilia and hyperreactivity, but did not affect the IgE antibody production.Conclusion These results suggest that the inhibition of IgE production does not suppress the onset of airway hyperreactivity and eosinophilia in mice, and that IFN‐γ inhibits the antigen‐induced airway hyperreactivity, probably due to the inhibition of airway eosinophilia.