ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00568.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00569.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00570.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundDendritic cells (DC) are the most potent antigen‐presenting cells (APC) and stimulators of T cells. Dendritic cells are also likely to be essential for the initiation of allergic immune responses in the lung. However, there are not many data on the presence of dendritic cells in the airways of patients with atopic asthma and on the effects of corticosteroid‐treatment on such dendritic cells.ObjectiveWe investigated the distribution of dendritic cells in the bronchial epithelium and mucosa of 16 non‐smoking atopic asthmatic patients and eight healthy control subjects using detailed immunohistochemistry (CD l a, HLA‐DR, L25 as markers for dendritic cells).MethodsEleven asthmatics were treated for 2.5 years with bronchodilators only and five with bronchodilators and inhaled beclomethasone dipropionate (BDP), 800 μg daily. The patients were randomly sampled from a double‐blind multicentre study. Results There were higher numbers of CD la+DC (P =0.003), L25+DC (P =0.002) and HLA‐DR expression (P =0.042) in the bronchial mucosa of asthmatic patients compared with healthy controls. After 2.5 years of treatment, we found a significant increase in fiow expiratory volume in I second (FEV1) (P =0.009) and a significant decrease in hyperresponsiveness (PC20histamine) (P=0.013) in the corticosteroid group (n =5) compared with the bronchodilator group (n= 11). This dinical improvement in the corticosteroid‐treated group was accompanied by significantly lower numbers of CDla+DC (P = 0.008), and HLA‐DR expression (P‐ 0.028) in the bronchial mucosa than in the bronchodilator‐treated group.ConclusionOur data suggest that dendritic cells are involved in asthmatic inflammation and that corticosteroids may downregulute the

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00571.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundNeuropeptides are likely to be implicated in the pathophysiology of allergen‐induced airway responses. However, upon release in the airways, neuropeptides are potentially inactivated by neutral endopeptidase (NEP). Objective We hypothesized that NEP‐inhibition by inhaled thiorphan (TH) would increase allergen‐induced early (EAR) and late (LAR) asthmatic responses, and allergen‐induced airway hyperresponsiveness to histamine in asthmatic subjectsin vivo. The dose and dosing intervals of TH were derived from previous pharmacokinetic and dose‐finding studies.MethodsNine non‐smoking, atopic, asthmatic men with dual asthmatic responses to inhaled house‐dust mite extract participated in a double‐blind, placebo‐controlled, cross‐over study. During each study period PC20histamine was measured 24 h before, and 3 and 24 h post‐allergen. TH (1.25 mg/mL, 0.5 mL) or placebo (P) were aerosolized pre‐allergen, and three times at 2 h intervals post‐allergen (total dose of TH: 2.5mg). Forced expiratory volume in one second (FEV1) was recorded and expressed as percentage fall from baseline. The EAR (0–3 h) and the LAR (3–8 h) were defined as maximum percentage fall from the pre‐allergen baseline and as corresponding areas under the time‐response curves (AUC).ResultsAs compared with P, TH failed to induce an acute effect on FEV1at any of the timepoints (P>0.08). There was no significant difference between P and TH in the EAR and the LAR: neither in terms of maximum percentage fall from baseline (mean± SEM: EAR: 22.3 ±4.7% (P) and 20.4±4.1% (TH). P=0.75; LAR: 25.2 ± 4.7% (P) and 26.4±5.8% (TH), P=0.77) nor in terms of AUC (P =0.16). Correspondingly, the changes in PC20histamine were not different between the two treatments (F>0.40).ConclusionWe conclude that four adequate doses of the inhaled NEP‐inhibitor, thiorphan. failed to potentiate allergen‐induced airway responses in asthma. These results suggest that either neuropeptides do not play a predominant role in allergeninduced airway responses, or that allergen challeng

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00572.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundAllergy to rats is an important occupational health problem. The allergens of rat urine have been well defined but those in rat room dust, a potentially important source of inhalant exposure, have not.ObjectiveTo describe the allergens present in rat room dust and to identify a suitable marker protein which may be used to quantify airborne rat allergen. Methods Dust collected from the air‐conditioning system (bulk dust, ‘bd’) and with an air sampler (airborne dust, ‘ad’) were analysed by radioallergosorbent test (RAST) inhibition, immunoblotting and immunoblot inhibition techniques and comparisons made with hair and urine extracts prepared from adult male Wistar rats. Results Extensive crossreactivity was found between the extracts by RAST inhibition under different experimental conditions. Dust was more potent as an inhibitor than other extracts. The immunoblotting patterns of both dusts were similar although ‘ad’ contained an allergen at 29kDa not found in ‘bd’. Forty‐two sera from rat allergic subjects were used to identify 18 allergens in ‘bd’. Three ‘major’ allergens were found; 100% of subjects had immunoglobulin (Ig)E to a 44 kDa allergen and 74% and 88% of subjects had IgE with bound to the 20.5 and 17 kDa allergens respectively. Immunoblot inhibition experiments identified the 17 kDa dust allergen as α2u‐globulin (Rat nI). Conclusions Rat dust is a complex allergenic source. The 17 kDa dust allergen has immunological identity with Rat nl and is a suitable marker protein for the quantit

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00573.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundHigh prevalences of work‐related respiratory symptoms in relation to organic dust exposure have been reported in the potato processing industry, but the responsible effect mechanisms are not known.ObjectiveTo study the possible role of a type III allergy in aetiology.MethodsSpecific immunoglobulin G (IgG) and IgG4subclass antibodies against occupational airborne antigens were determined in sera from 131 potato processing workers and 36 non‐exposed controls. Personal exposure to airborne antigens was measured, and a preliminary biochemical characterization was carried out.ResultsSpecific IgG was detectable in almost all sera, but levels were significantly (P<0.01) higher in potato processing workers compared with controls. Specific IgG4was detectable in half of the workers' sera, but in none of the control sera. The antigens involved appeared to be heat‐labile potato proteins. Antibody levels increased during the processing campaign in most workers, and this increase was dependent on the level of antigen exposure. Both the difference in IgG titres between the occupationally exposed group and the non‐exposed group, and the exposure‐related increase in specific IgG titres seemed to be mainly due to specific antibodies of the IgG4subclass. Specific antibodies showed a non‐significant tendency to lower levels in workers with work‐related respiratory symptoms.ConclusionOccupational respiratory exposure in the potato processing industry leads to a strong humoral immune response, most pronounced for lgG4subclass antibodies. Type III allergy is, however, unlikely to play a predominant role in the aetiology of respir

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00574.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundThe two main features of asthtna are bronchial hyperresponsiveness and inflammation. The inflammatory response in asthma consists of infiltration and activation of a variety of inflammatory cells including neutrophils. Our previous studies have shown that stimuhited neutrophil supernatants cause hyperresponsiveness of human bronchial tissuein vitro.ObjectiveTo investigate the effect of the sensitization status of the tissue and the albumin concentration used to prepare supernatants on the response of human bronchial tissue to stimulated neutrophil supernatants.MethodsNeutrophil supernatants were prepared from human isolated blood in the presence of varying concentrations of albumin (0%, 0.1% and 4%), Neutrophil supernatants were added to sensitized and non‐sensitized human isolated bronchial tissue which was stimulated with electrical field stimulation (EFS) (20 s every 4min). Receptor antagonists specific for the prostaglandin and thromboxane (10−7M GR3219I), platelet activating factor (10−6M WEB 2086), leukotriene D4(10−6M MK‐679) and neurokinin A (10−7M SR48968) receptors were used to identify neutrophil products responsible for the effects observed in the bronchial tissue. Results In non‐sensitized human bronchial tissue, stimulated neutrophil supernatants induced a direct contraction in the presence of 0% and 0.1 % but not 4% albumin. This contraction was due to leukotriene D4as MK‐679 completely inhibited the contraction. In contrast, stimulated neutrophil supernatants increased responsiveness of sensitized human bronchial tissue to EFS. The increased responsiveness was observed only in the presence of 0.1% albumin, with the site of modulation likely to be prejunctional on the parasympathetic nerve. The increased responsiveness was not inhibited by any of the antagonists tested.ConclusionSensitization status of the tissue and albumin concentration effect the responsiveness of human bronchial tissue to stimulated neutrophil supernatant. Our results suggest a possible role for neutrophils in hype

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00575.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundWe have shown that interleukin‐5 (IL‐5) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) are present in sputum from patients experiencing acute asthma attacks, by eosinophil survival assay. The viability of guinea‐pig eosinophils was significantly increased in the presence of such sputum extracts after 3 days' culture, and it was inhibited by the addition of anti‐IL‐5 and anti‐GM‐CSF antibodies. However, the contribution of IL‐5 to the increase in eosinophil viabihty was less than expected from the values of IL‐5 measured by enzyme‐linked immunosorbent assay (ELISA). Therefore, we speculated that something in sputum inhibited the function of IL‐5.ObjectiveTratnsforming growth factor‐β (TGF‐β) was the only cytokine we tested that inhibited the prolongation of survival of guinea‐pig eosinophils induced by IL‐5. The objective of this study is to detect TGF‐β in the same sputum.MethodsGuinea‐pig eosinophils were cultured with or without anti‐TGF‐β antibody in the presence of sputum extracts, and the eosinophil viability was counted after 3 days. Measurement of TGF‐βlin sputum was performed by ELISA.ResultsEosinophil viabilities with and without anti‐TGF‐β antibody were 79.7 ± 2.9% and 69.0 ± 2.7%, respectively, and the difference between them was statistically significant (P<0.05, n = 9). The concentration of TGF‐β1in the sputum was 21.7 ± 3.3 ng/mL (n = 9).ConclusionThese observations suggest that T

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00576.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundThe need to develop predictive tests which could identify potential allergens has been recognized for many years. There is as yet no acceptedin vitromethod for the assessment of contact sensitizers.ObjectiveWe have tested the ability of a range of contact allergens to inducein vitroprimary sensitization of autologous T cells.MethodT‐cell proliferation induced by haptens using 2‐day cultured human Langerhans cells as antigen‐presenting cell was assessed by3H thymidine incorporation. Antigen specific stimulation was calculated as stimulation indexes.ResultsStrong allergens inducedin vitroa primary T‐cell response in all (trinitrophenyl, TNP: 13/13) or in the majority (fluorescein isothiocyanate, FITC:7/10) of experiments. An irritant, sodium dodecyi sulfate (SDS). failed to generate a significant T‐cell proliferation in any of the experiments (0/10). We obtained a significant lymphoproliferative response to weak sensitizers only in a limited number of experiments: (coumarin:1/12, citronellal: 0/10, hydroxycitronellal: 2/8). p‐Phenylenediamine (PPDA), a prohapten and highly sensitizing chemicalin vivo, generated primary sensitizationin vitroin only one of six experiments, while Bandrowski's base (BB), a metabolization product of PPDA induced a significant T‐cell response in all six experiments.ConclusionThe presentin vitromodel allows discrimination between two groups of substances: strong contact sensitizers (TNP, FITC. BB) on the one hand and weak sensitizers (coumarin, citronellal and hydroxycitronellal) and irritants (SDS) on the other hand. It could be used as a screeningin vitroassay to eliminate strong contact allergens before further predictive animal tests have to

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00577.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY