bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lectins interact differentially with purified human eosinophils, cultured cord blood‐derived mast cells and the myeloid leukaemic cell line AML14.3D10: induction of interleukin‐4 secretion is conserved among granulocytes, but is not proportional to agglutination or lectin–glycoprotein interaction
Authors: Hoffmann H. J. , Dahl C. , Schiøtz P. O. , Berglund L. , Dahl R. 
Published: July 2003

SummaryBackground Atopy is closely associated with the cellular T helper type‐2 (Th2) phenotype, that is dominated by the pleiotrophic cytokine IL‐4. The cellular source of IL‐4 has yet to be determined, although basophils have been proposed. Eosinophils and mast cells are likely contenders investigated here, and the eosinophil‐like leukaemia line AML14.3D10 is compared to eosinophils as an in vitro culturable model for eosinophils. Lectins can cross‐link‐specific surface glycoproteins and are found in the ingested (processed foods) and inhaled (airborne pollen grains) human environment. Therefore it is of interest to determine whether lectins can elicit the release of IL‐4 from Th2‐associated granulocytes other than basophils.Method This study investigated the ability of eosinophils, AML14.3D10 and mast cells to secrete preformed IL‐4 in response to stimulation with lectins, and explored molecular mechanisms underlying the interaction.Results Purified eosinophils and basophils, and cultured mast cells and AML14.3D10 cells were incubated with 1 µm lectin. Agglutination was scored by microscopy. IL‐4 secretion was measured by enayme‐linked immunosorbent assay. Biotinylated lectins were used to determine binding to cells by flow cytometry and in lectin blots of sodium dodecyl sulphate (SDS) gels.Discussion Purified human eosinophils, AML14.3D10 cells and cultured mast cells secrete IL‐4 with a pattern similar to that found in basophils when stimulated with a panel of reactive and unreactive lectins. The lectin SNA induces IL‐4 secretion from mast cells and basophils, but not from eosinophils or AML14.3D10. Eosinophils appear to secrete only pre‐formed IL‐4, whereas mast cells may synthesize IL‐4 on ligation with the lectin LCA. Lectins that agglutinate the granulocytes investigated do not necessarily induce secretion of IL‐4. Lectins that elicit secretion of IL‐4 bind more to eosinophils than unreactive lectins as determined by flow cytometry and lectin blotting of SDS gels.Conclusion As granulocytes with functions related to that of basophils, eosinophils, AML14.3D10 and cultured mast cells respond to stimulation with lectins similarly to basophils. This emphasizes the possibility that eosinophils and mast cells may be linked in their cellular heritage as the cellular partners, and lectins as ligands, may contribute to the maintenance of a Th2‐favoured microenvironment that is thought to underlie the allergic march.
Monitoring of seasonal variability in bronchial hyper‐responsiveness and sputum cell counts in non‐asthmatic subjects with rhinitis and effect of specific immunotherapy
Authors: Polosa R. , Li Gotti F. , Mangano G. , Mastruzzo C. , Pistorio M. P. , Crimi N. 
Published: July 2003

SummaryBronchial hyper‐responsiveness (BHR) is documented in a proportion of non‐asthmatic individuals with allergic rhinitis (NAAR) and reflects inflammatory events in the lower airways. Natural exposure to allergens is known to modulate BHR and the level of airway inflammation in asthma, but less consistently in NAAR. Specific immunotherapy (SIT) attenuates symptoms possibly by reducing BHR and airway inflammation. The influence of natural exposure to Parietaria pollen on BHR and sputum cell counts of NAAR was investigated and the effect of Parietaria SIT examined. Thirty NAAR, monosensitized to Parietaria judaica, participated in a randomized, double‐blind, placebo‐controlled, parallel group study of the effects of a Parietaria pollen vaccine on symptoms/medication score, BHR to inhaled methacholine and adenosine 5′‐monophosphate (AMP), and cell counts in the sputum collected out of and during the pollen seasons for 36 months. Seasonal variation in BHR to inhaled methacholine and AMP and changes in sputum cell counts were documented. Changes were consistent for AMP, but not methacholine, and invariably associated with modifications in sputum eosinophils and epithelial cells. The clinical efficacy of Parietaria SIT was associated with a decline in the seasonal deterioration of BHR to AMP, whereas no significant effect was observed on BHR to methacholine or sputum cell differentials. Between‐groups comparison of the seasonal changes in PC15 methacholine values and sputum cell differentials calculated as the AUC were not statistically significant, whereas a significant difference in PC15 AMP was demonstrated throughout the study (P=0.029), the median (inter‐quartile range) AUC values being 2478.5 (1153.3–3600.0) and 1545.5 (755.3–1797.9) for the SIT‐ and placebo‐treated group, respectively. Bronchial airways of NAAR exhibit features of active inflammation that deteriorate during natural allergen exposure, particularly with regard to BHR to AMP. The clinical efficacy of Parietaria SIT was exclusively associated with attenuation in seasonal worsening of PC15 AMP, suggesting that AMP may be useful in monitoring changes in allergic inflammation of the airways.
Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics
Authors: Ricciardolo F. L. M. , Stefano A. Di , Krieken J. H. J. M. van , Sont J. K. , Schadewijk A. van , Rabe K. F. , Donner C. F. , Hiemstra P. S. , Sterk P. J. , Mauad T. 
Published: July 2003

SummaryBackground
The mechanisms that regulate epithelial integrity and repair in asthma are poorly understood. We hypothesized that allergen exposure could alter epithelial inflammation, damage and proliferation in atopic asthma.Objective
We studied epithelial cell infiltration, shedding, expression of the proliferation marker Ki‐67 and the epithelial cell–cell adhesion molecules Ep‐CAM and E‐cadherin in bronchial biopsies of 10 atopic mild asthmatics 48 h after experimental diluent (D) and allergen (A) challenge in a cross‐over design.Methods
Epithelial shedding, expressed as percentage of not intact epithelium, Ki‐67+, eosinophil/EG‐2+, CD4+ and CD8+ cells were quantified by image analysis in bronchial epithelium, and adhesion molecules were analysed semi‐quantitatively.Results
Epithelial shedding was not altered by A (D: 88.1±3.1% vs. A: 89.2±3.7%; P=0.63). The numbers of Ki‐67+ epithelial (D: 10.2±0.2 vs. A: 19.9±0.3 cells/mm; P=0.03), EG‐2+ (D: 4.3±0.5 vs. A: 27±0.3 cells/mm; P=0.04) and CD4+ cells (D: 1.7±1.2 vs. A: 12.3±0.6 cells/mm; P=0.04) were significantly increased after A, whilst CD8+ numbers were not significantly changed (P>0.05). E‐cadherin and Ep‐CAM epithelial staining showed a similar intensity after D and A (P>0.05). We found a positive correlation between EG‐2+ and Ki‐67+ cells in the epithelium (Rs: 0.63; P=0.02).Conclusion
Our study indicates that allergen challenge increases epithelial proliferation in conjunction with inflammation at 2 days after exposure. This favours the hypothesis that long‐lasting epithelial restitution is involved in the pathogenesis of asthma.
Effects of cysteinyl leukotrienes in small human bronchus and antagonist activity of montelukast and its metabolites
Authors: Mechiche H. , Naline E. , Candenas L. , Pinto F. M. , Birembault P. , Advenier C. , Devillier P. 
Published: July 2003

SummaryBackground  Evidence suggests that small airways contribute to clinically significant processes in asthma. Cysteinyl leukotrienes (CysLTs) are considered to be pivotal mediators in the pathogenesis of asthma. Montelukast (MK), a specific CysLT1 receptor antagonist, is metabolized in two main hydroxylated metabolites (termed M5 and M6, respectively).Objectives  The aims of this study were to compare the responsiveness of small and large human bronchi to the three CysLTs, to evaluate the antagonist activity of MK, M5 and M6 in these preparations of human bronchi, and to characterize the CysLT receptors involved in the contractile response.Methods and results  In isolated small bronchus (i.d. 0.5–2 mm), the potencies (−log molar EC50) of LTC4, LTD4 and LTE4 were 9.3 (n=11), 9.1 (n=30) and 8.4 (n=14), respectively. The three CysLTs were about 30‐fold more potent in small bronchi than in larger bronchi (i.d. 4–6 mm). In small bronchi, MK significantly shifted to the right the CysLT concentration–effect curves with pA2 values against LTC4, LTD4 and LTE4 of 9.1 (n=3), 9.0 (n=11) and 8.7 (n=5), respectively. The antagonist potencies of M6 and M5 were similar to MK and fivefold lower, respectively. A similar activity of MK against the three CysLTs suggested that CysLT1 receptors are involved in the contraction of human bronchus. Analysis by RT‐PCR also indicated that human bronchus mainly expressed CysLT1 receptors.Conclusion  MK exerts a potent antagonist activity against the particularly potent constricting effects of CysLTs in isolated human small bronchi, which only expressed the CysLT1 receptor subtype. The metabolites of MK are also potent in vitro antagonists, but may not participate in the therapeutic activity of MK due to their low plasma concentrations in patients treated with the recommended dose of MK.
Eosinophils from patients with asthma express higher levels of the pan‐leucocyte receptor CD45 and the isoform CD45RO
Authors: Blaylock M. G. , Lipworth B. J. , Dempsey O. J. , Duncan C. J. A. , Lee D. K. C. , Lawrie A. , Douglas J. G. , Walsh G. M. 
Published: July 2003

SummaryBackground
Eosinophils and their secreted mediators are heavily implicated as effector cells in asthma and other allergic diseases. Comparisons were made between expression of CD45, CD45RA, CD45RB and CD45RO by eosinophils from asthmatic patients and non‐asthmatic atopic and non‐atopic, non‐asthmatic control subjects.Methods
Twenty‐seven patients with asthma and 33 control subjects were recruited for the study. Eosinophil expression of CD45, CD45RA, CD45RB and CD45RO was established by immunostaining and flow cytometry was performed on whole leucocyte samples. Eosinophil apoptosis in response to CD45 and CD45 isoform monoclonal antibody (mAb)‐dependent receptor ligation was assessed by binding of annexin V and flow cytometry.Results
Eosinophils from patients with asthma expressed significantly (P<0.05) higher levels of pan‐CD45 and CD45RO compared with eosinophils from non‐asthmatic, non‐atopic subjects. No significant correlations were found between expression of either pan‐CD45 or CD45RO and the degree of symptoms in the asthmatic patients as defined by lung function (FEV1 and FEF25–75) and methacholine PD20. Increased expression of pan‐CD45 or CD45RO did not appear to be a consequence of the atopic phenotype. Higher expression of pan‐CD45 or CD45RO by eosinophils from asthmatic patients was not associated with greater sensitivity to CD45 and CD45RO mAb receptor ligation‐induced eosinophil apoptosis.Conclusion
Higher expression of CD45 and CD45RO by eosinophils from asthmatic patients appeared to be a consequence of asthma rather than atopy and further supports a role for activated eosinophils in asthma.
ELISpot: a new tool for the detection of nickel sensitization
Authors: Lindemann M. , Böhmer J. , Zabel M. , Grosse‐Wilde H. 
Published: July 2003

SummaryBackground
The standard assay for the clinical detection of contact allergy against nickel is the patch test. For research purposes, the in vitro lymphocyte transformation test (LTT) is mostly applied. However, the in vivo application of allergens includes the potential of sensitization, whereas the LTT demands 6 days of cell culture and radioactive labelling procedures.Objective
The purpose of this study was to validate an enzyme‐linked immunospot (ELISpot) assay to specifically detect cellular response against nickel sulphate in correlation with patch test, anamnestic data, and LTT results.Methods
In probands with positive (n=60) and negative patch test results (n=19), cytokine ELISpot and LTT were performed in parallel using various concentrations of nickel sulphate, various numbers of responding peripheral blood mononuclear cells (PBMC), and various durations of cell cultures.Results
Concentrations of 50 and 75 μM nickel sulphate were found to be optimal to stimulate in the ELISpot 4×105 and in the LTT 2×105 PBMC, respectively. An increase in ELISpot sensitivity was reached by pre‐incubation with nickel sulphate for 24 h prior to transfer to ELISpot plates. In nickel‐sensitive probands, an average precursor cell frequency of 19×105, 1.7×105, and 0.7×105 could be defined for IFN‐γ, IL‐2, and IL‐4 producing PBMC, respectively. In non‐sensitive probands IFN‐γ producing cells were detectable, but with significantly lower frequency (2×105; P=0.004). The prior performance of patch tests had no significant effect on cytokine production or lymphocyte proliferation. Overall, the parameters patch test, anamnestic nickel allergy, ELISpot, and LTT results were positively correlated (P<0.05).Conclusions
Based on these experiments, the quantitative in vitro detection of cell‐mediated reactions towards nickel as well as other heavy metal ions should be possible utilizing the above‐described ELISpot assay.
Adenoviral interleukin‐12 gene transduction into human bronchial epithelial cells: up‐regulation of pro‐inflammatory cytokines and its prevention by corticosteroids
Authors: Ogawa H. , Nishimura N. , Nishioka Y. , Azuma M. , Yanagawa H. , Sone S. 
Published: July 2003

SummaryBackground
One of the potential effects of IL‐12 is to restore Th1/Th2 balance. Therefore, we investigated the possibility of developing a system for local delivery of IL‐12 into the airways by examining protein expression in a human bronchial epithelial cell line (BEAS‐2B) after adenoviral IL‐12 gene transduction. The effects of dexamethasone on the gene‐modified cells were also examined.Mehods
Adenoviral vectors AxCAegfp and Ax1CIhp40ip35 were used to transduce enhanced green fluorescence protein and IL‐12 genes, respectively, into BEAS‐2B cells. Wild‐type and IL‐12 gene‐transduced BEAS‐2B cells were then incubated with or without dexamethasone, and concentrations of IL‐12, IFN‐γ, IL‐6, IL‐8, granulocyte macrophage‐colony stimulating factor and chemokines (TARC and RANTES) in the supernatant were measured by ELISA. IL‐12 receptor expression was analysed by flow cytometry and RT‐PCR.Results
The efficiency of transgene expression in BEAS‐2B cells at a multiplicity of infection of 30 was approximately 80%. Gene‐modified BEAS‐2B cells produced biologically active IL‐12, regardless of dexamethasone treatment. While IL‐12 gene transduction led to increased production of IL‐6 and IL‐8 by BEAS‐2B cells, expressions of these proteins were suppressed by dexamethasone. Addition of exogenous IL‐12 failed to augment BEAS‐2B cell IL‐6 and IL‐8 production, and IL‐12 receptor expression by BEAS‐2B cells was not detected.Conclusions
Our findings suggest that adenoviral IL‐12 gene transduction may be effective in inducing IL‐12 expression in the airways, and could be a potential approach in the management of bronchial asthma.
No evidence for association between the −112G/A polymorphism of UGRP1 and childhood atopic asthma
Authors: Jian Z. , Nakayama J. , Noguchi E. , Shibasaki M. , Arinami T. 
Published: July 2003

SummaryBackground
Susceptibility to asthma is known to involve genetic factors. Genome‐wide screens have indicated that the chromosome 5q31–q34 region is linked to and/or associated with asthma. A new gene, named UGRP1 and reported by Niimi et al., encodes uteroglobin‐related protein and is expressed in the lung and trachea. Niimi et al. showed the −112G/A polymorphism of the UGRP1 gene to be associated with asthma in a case–control study.Objective
The objective of the present study was to replicate this association and confirm the possible role of the UGRP1−112G/A polymorphism in the aetiology of childhood asthma in a Japanese population.Methods and results
We conducted a transmission disequilibrium test (TDT) in 131 families identified through paediatric patients being treated for asthma. A case–control study was also carried out by comparing the probands and 137 unrelated non‐atopic non‐asthmatic Japanese children and 211 unrelated healthy Japanese adults. The −112G/A polymorphism was genotyped by the PCR‐RFLP method. The TDT revealed that the −112A allele was not preferentially transmitted to asthma‐affected children (P=0.85). Neither the presence of at least one A allele in an individual's genotype (sum of the G/A and A/A genotypes) nor the −112A allele was more prevalent among the asthma subjects than among the control subjects.Conclusion
Our findings indicate that the UGRP1−112G/A polymorphism does not play a substantial role in genetic predisposition to childhood asthma in this Japanese population.
Cross‐reactivity between Ficus benjamina latex and fig fruit in patients with clinical fig allergy
Authors: Focke M. , Hemmer W. , Wöhrl S. , Götz M. , Jarisch R. 
Published: July 2003

SummaryBackground  Anaphylactic reactions to fig fruits (Ficus carica) have been reported from subjects sensitized to Ficus benjamina (FB) latex allergens. Figs may also be involved in the latex–fruit syndrome.Objective  To study the immunologic relationship between fig fruit, Ficus benjamina, natural rubber latex (Hevea brasiliensis), and other tropical fruits.Methods  RAST inhibition and Western blotting with FB and fruit extracts was performed in five patients with oral allergy syndrome (OAS) or anaphylaxis after the ingestion of figs and one patient with symptoms from exposure to FB trees. Co‐sensitization to rubber latex and tropical fruits (kiwi, banana, avocado, papaya, pineapple, mulberry) was studied by skin testing.Results  RAST to FB was inhibited >95% by FB extracts and 16–65% (mean 49%) by extracts from fresh fig. RAST to fig fruit was inhibited >95% by FB and fresh fig, 63–97% (mean 86%) by dried fig, and 0–84% (mean 35.5%) by kiwi fruit. FB and fig extracts lost most of their allergenicity when denatured by heat (95 °C) or reduced by dithiothreitol. Western blotting after non‐reducing gel electrophoresis revealed IgE binding to proteins of 22 and 28–34 kDa in FB latex; however, no corresponding allergens could be detected in fig extracts. Positive skin tests were obtained most often with kiwi fruit, papaya, and avocado. Sensitization to rubber latex could not be demonstrated in any of the patients. RAST to papain was positive in three of five patients.Conclusions  Allergic reactions to fresh or dried figs can present as a consequence of primary sensitization to airborne FB allergens independent of sensitization to rubber latex allergens. Kiwi fruit, papaya, and avocado as well as pineapple and banana may be other fruits associated with sensitization to Ficus allergens.
Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal responsiveness in seasonal allergic rhinitis
Authors: Lee D. K. C. , Carstairs I. J. , Haggart K. , Jackson C. M. , Currie G. P. , Lipworth B. J. 
Published: July 2003

SummaryBackground
Butterbur (BB) or Petasites hybridus, a herbal remedy, exhibits in vitro inhibition of cysteinyl leukotriene biosynthesis. However, no placebo‐controlled studies have been performed to evaluate the effectiveness of BB on objective outcomes such as nasal provocation testing in seasonal allergic rhinitis (SAR).Methods
Twenty patients with grass‐pollen‐sensitized SAR were randomized in a double‐blind, cross‐over manner to receive for 2 weeks either BB 50 mg twice daily or placebo (PL) twice daily during the grass pollen season. Nasal adenosine monophosphate (AMP) challenge (the primary outcome) was administered as a single 400 mg/mL dose after each randomized treatment.Results
Spontaneous recovery following AMP challenge (area under the response time profile curve as %.min±SEM) was significantly attenuated (P=0.028) with BB (584±289) compared to PL (1438±240); mean difference: 854 (95% CI 95–1614), and the maximum % peak nasal inspiratory flow reduction from baseline following AMP challenge was significantly blunted (P=0.036) with BB (30±4) compared to PL (43±5); mean difference: 13 (95% CI 1–25).Conclusions
BB exhibited protection against AMP‐induced nasal responsiveness during the grass pollen season in sensitized patients. This is turn may explain its potential clinical efficacy in patients with SAR.
Quantitative measurement of airborne allergens from dust mites, dogs, and cats using an ion‐charging device
Authors: Custis N. J. , Woodfolk J. A. , Vaughan J. W. , Platts‐Mills T. A. E. 
Published: July 2003

SummaryBackgroundIncreasing evidence suggests that children raised with an animal(s) in the house have a decreased risk of becoming sensitized. However, it is not clear whether this phenomenon is related to airborne exposure.ObjectiveTo estimate airborne exposure to animal dander and dust mite allergens using a device that can sample large volumes of air silently.MethodsThe device, which uses an ion‐charging technique to move air and to collect particles, was run at 1.7 m3/min for 24 h in 44 homes with and without animals. The allergen collected was measured by ELISA for Fel d 1, Can f 1, Der p 1, and Der f 1.ResultsAirborne Fel d 1 was present in all homes with a cat (n=27). The quantities measured, i.e. 0.5–20 μg in 24 h, represent 0.01–0.3 μg Fel d 1 inhaled/day at normal breathing rates (20 L/h). Values for houseswithouta cat were 0.01–0.05 μg inhaled/day. Airborne Fel d 1 correlated significantly with floor Fel d 1 (r=0.58,P<0.001). Results for Can f 1 were similar in houses with a dog, but this allergen was only detected airborne in two houses without a dog. Neither Der p 1 nor Der f 1 (i.e. <0.01 μg) was detected, which represents  1 ng inhaled/day during normal domestic activity. During disturbance airborne mite was detected with both the ion‐charging device and a filter run in parallel. For cat and mite allergens there was a close correlation between the two techniques (r=0.84,P<0.001).ConclusionExposure to cat or dog allergen airborne in homes with an animal can be up to 100 times higher than exposure to mite allergen. The results are in keeping with a model where immunological tolerance to animal dander allergens results from high exposure.
The major Platanus acerifolia pollen allergen Pla a 1 has sequence homology to invertase inhibitors
Authors: Asturias J. A. , Ibarrola I. , Eraso E. , Arilla M. C. , Martínez A. 
Published: July 2003

SummaryBackground
Sycamores or plane trees are an important source of airborne allergens in many cities of the United States and Western Europe. Pla a 1 has been described as a major allergen from Platanus acerifolia (London plane tree).Objective
To clone and characterize the cDNA for Pla a 1 and to express the recombinant protein.Methods
Pla a 1 was isolated by cationic exchange, gel filtration, and reverse‐phase chromato‐graphies. Pla a 1 cDNA was cloned by reverse transcription followed by polymerase chain reaction, using amino acid sequences from tryptic peptides of the allergen. The Pla a 1 encoding sequence has been subcloned into the pKN172 expression vector and expressed in Escherichia coli as a non‐fusion protein. Purified recombinant protein has been tested for its IgE‐binding capacity in immunoblot, immunoblot inhibition, and ELISA.Results
Pla a 1 reacted with serum IgE from 35 of the 42 (83.3%) Platanus‐allergic patients studied and represented 60% of the total IgE‐binding capacity of the P. acerifolia pollen extract. The allergen displayed 43% sequence identity to a grape invertase inhibitor and showed a predicted secondary structure characteristic of all‐alpha proteins. Serological analysis revealed that both natural and recombinant forms of Pla a 1 displayed similar IgE‐binding capacity.Conclusions
Pla a 1 belongs to a new class of allergens related to proteinaceous invertase inhibitors. Recombinant Pla a 1 binds IgE in vitro like its natural counterpart and, therefore, it can be useful for specific diagnosis and structural studies.