ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00584.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.tb00585.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.tb00586.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.tb00587.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundA family history of atopy, and cord blood immunoglobulin E concentration, have been shown to be predictors of atopic disease in children. Several studies have suggested that parental atopy may be related to newborn immunoglobulin E.ObjectiveThe purpose of our analysis was to evaluate whether parental history of allergic disease was associated with cord blood immunoglobulin E concentration.MethodsThe study subjects were from a defined population of 777 newborns delivered between 1987 and 1989. The mothers of these children completed a questionnaire during pregnancy concerning themselves and the child's father, including parental history of physician diagnosis of allergic diseases (allergies, hay fever and asthma). Total immunoglobulin E levels were quantitated in cord blood samples with an enzyme‐hnked immunoassay.ResultsMedian cord blood immunoglobulin E concentration was higher among infants whose mothers had a history of atopic disease, particularly for those with a history of asthma (P<0.022) and allergen immunotherapy (P<0.016) vs infants whose mothers had no history of any atopic disease. Comparing all babies with a maternal history of asthma, to babies where neither parent had a history of any atopic disease, the median cord blood immunoglobulin E was significantly higher (0.36IU/mL vs 0.21 IU/mL;P<0.009). This association was found only among female infants (0.49IU/mL vs 0.20 IU/mL;P<0.001).ConclusionMaternal, but not paternal, history of atopic disease was associated with an elevated immunoglobulin E among newborns. For maternal asthma, this association was only evident in infant girl

ISSN:0954-7894    

DOI:10.1046/j.1365-2222.1996.1024365.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundThe high affinity receptor for IgE (FcεRI) has recently been identified on antigen presenting cells, i.e. Langerhans cells and monocytes from atopic donors and it was hypothesized that FcεRI expression levels correlated with allergy.ObjectiveThe aims of the study was to investigate the function and expression of FcεRI on monocytes frotn non‐atopic donors.MethodsPurified monocytes or peripheral blood mononuclear cells were used to study FcεRI expression and signal transduction on CD14 positive cells by flow cytometry and/or confocal laser microscopy.ResultsFreshly isolated monocytes from healthy individuals (n = 58) were shown to express FcεRI (median 18%, range 2–66%). No IgE was bound to these receptorsin vivo, andin vitrono significant binding of complete IgE molecules could be obtained. IgE positive monocytes from atopic donors were also found to have free FcεRI, incapable of binding IgEin vitro. Oti all CD14 positive cells free FcεRI expression was rapidly and completely lost during culture in conventiotial culture media (IMDM. RPMI) but not in phosphate buffered saline (PBS). Moreover, signal transduction through free FcεRI appeared to be inhibited. However, both IgE binding and calcium mobilization were restored by treatment of fresh non‐atopic monocytes with neuraminidase. Importantly, culturing these monocytes overnight in conventional medium containing 2μg/mL IgE induced a cycloheximide insensitive accumulation of IgE bound to FcεRI and, in addition, led to cell activation.ConclusionMonocytes from both atopic donors and healthy individuals express FcεRI, but the previously reported different expression levels between the two groups seem to be directly related to the absence or presence of TgE in the serum. This may be due to the fact that FcεRI is subjected to a constant turnover process which is slowed down but not prevented by ligand binding. In addition, free FcεRI on non‐atopic monocytes are under control of a neuramindase sensitive structure(s), which influences signal transduc

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00589.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackground and objectiveIn order to study the role of mast cells and IL‐5 in allergen‐induced airway hyperreactivity in mice, airway responsiveness in WBB6F1‐W/Wvmice (mast cell deficient) and the effects of anti‐IL‐5 monoclonal antibody (NC‐17) and three anti‐allergic drugs (N‐556, ketotifen and amlexanox) on airway hyperreactivity in Balbc mice were studied.MethodsMice 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 acetyleholine was measured and broncho‐alveolar lavage fluid (BALF) was obtained.ResutlsThree inhalations of OA caused an increase in leucocytes (including eosinophils). accompanied by increases in IL‐5 in BALF, and airway hyperreaetivity to acetylcholine in Balb/c and WBB6F1‐ +/+ mice. In WBB6F1‐W/Wvmice, antigen inhalation resulted in increases in leucocytes and IL‐5 in BALF but did not result in airway hyperreactivity. NC‐17 at doses between 10 and 20μg (intratracheal injection) inhibited the antigen‐induced eosinophilia but did not affect airway hyperreaetivity in Balb/c mice. Three ‘anti‐allergie’ drugs clearly inhibited antigen‐induced increases in IL‐5 levels and the number of eosinophils in BALF, but did not alTect airway hyperreactivity in Balb/c mice.ConclusionsThese data suggest that mast cells play an important role in the onset of airway hyperreactivity but do not play a role in the productionofIL‐5 and eosinophilia. Furthermore., indicate that the inhibition of IL‐5 is not always associated with a reduetion in

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00590.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundImmunoglobulin E (IgE) plays an important role in asthma, with total serum IgE levels closely related to both clinical expression of the disease and airway hyperresponsiveness. IgE binds to a high affinity cell‐surface receptor (FcεRI) which is present on mast cells and which has also recently been demonstrated on cutaneous dendritic cells. If pulmonary dendritic cells were also able to express this receptor, this would have important implications with regard to their potential role in asthma.ObjectivesThe aims of the study were to investigate the expression of the α subunit of the high affinity IgE receptor (FcεRI‐α) in normal and asthmatic airways, and to analyse its cellular provenance with particular emphasis on the dendritic cell.MethodsBronchial biopsy specimens were obtained using fibreoptic bronchoscopy from 10 atopic asthmatics and nine non‐atopic non‐asthmatic control subjects. Specimens were processed into glycolmethacrylate resin and analysed by immunohistochemistry using specific monoclonal antibodies against FcεRI‐α. and against tryptase and CDla. markers for mast cells and dendritic cells, respectively.ResultsThe numbers of dendritic cells were significantly higher in the airways of asthmatics compared with those of control subjects (P<0.02). Analysis of sequential sections revealed that the α subunit of FcεRI was localized to both mast eells and dendritic cells. The proportion of dendritic cells expressing FcεRI‐α was significantly inereased in the asthmatic group (P<0.003).ConclusionThese results support the hypothesis that dendritic cells play an important role in allergic asthma although the functional significance of FcεRI‐α expression ne

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00591.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundTreatment of aliergic asthma with inhaled corticosteroids, such as budesonide (BDN), results in downregulation of T‐cell activation and of eosinophil recruitment.ObjectiveSince blood concentrations of BDN, although significantly lower than those measured in the lung, may still have anti‐inflammatory effects, we evaluated the activity of BDNin vitroon: allergen‐induced release of lymphokines involved in eosinophil chemotaxis (i.e. IL‐3 and IL‐5), at drug concentrations similar to those obtainedin vivoin the lung (10−8M), and eosinophil locomotion, at ‘systemic concentrations’ of the drug (10−10M and 10−9M).MethodsTwenty‐three atopic asthmatic subjects (atopics) sensitized toDermatophagoides pteronyssinus(Dp) and seven non‐atopic healthy subjects (controls) were studied. Purified blood mononuclear cells (BMC) were stimulated with Dp, with or without BDN 10−8M and, after 6 days, the supernatants were collected and frozen to test their ehemotactie activity toward purified blood eosinophils and their levels of interleukin (IL)‐3 and IL‐5 by immunoassay. BMC were then pulsed for additional 18h with [3H]thymidine to evaluate allergen‐induced T‐cell proliferation. In addition, to test possible direct effects of ‘systemic concentrations’ of the drug on eosinophil locomotion, blood eosinophils were incubated for 1 h with BDN (10−10M and 10−9M) prior to test their ehemotactie response toward recombinant human IL‐3 and IL‐5.ResultsStimulation of BMC from atopies with Dp induced a statistically significant increase in [H]thymidine incorporation (P<0.05); secretion of ehemotactie factors for eosinophils (P<0.001) and the release of IL‐3 and IL‐5 (P<0.005 andP<0.05 respectively). BDN, at the concentration of 10−8M, was able to significantly down‐regulate T‐cell proliferation (P<0.05), the secretion of ehemotactie factors for eosinophils (P<0.001) and the release of IL‐3 and IL‐5 (P<0.01 andP<0.05 respectively). Similarly, “systemic concentrations” of BDN (10−10M and 10−9M) totally inhibited the ehemotactie response of blood eosinophils toward recombinant human IL‐3 and IL‐5 (P<0.005).ConclusionsConcentrations of BDN similar to those obtainedin vivoare effective in inhibiting both the release of eosinophils chemot

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00592.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundCold virus infections are associated with asthma attacks and with increased bronchial responsiveness even in normal subjects. Possible mechanisms include epithelial damage, interaction with adhesion molecules or with T‐helper cell subsets.ObjectiveTo determine whether colds increase lower airway inflammation, comparing atopic with non‐atopic normal subjects.MethodsThirty healthy volunteers (15 atopic) took part. Basehne tests included viral serology. microbiological culture and polymerase chain reaction for rhinovirus infection (HRV‐PCR), histamine bronchial provocation and bronchoscopy. Twenty subjects (eight atopic) underwent repeat tests when they developed a cold.ResultsForced expiratory volume in one second (FEV1) was significantly lower during colds (‐0.19L [95% confidence mterval ‐0.10, ‐0.29],P= 0,0004) and there was a significant increase in bronchial responsiveness (+0.62 doublings of the dose‐response slope [+0.24, +1.00],P=0.003). Eight subjects (two atopic) had a diagnosed viral infection: two HRV. three coronavirus (HCV), one HRV + HCV, one parainfluenza III(PI) and one respiratory syncytial virus (RSV) (alsoHaemophilus influenzae). In biopsies, during colds, total eosinophils (EG1+) increased significantly (geometric mean 6.73‐fold [1.12,40.46],P=O.04). Activated eosinophils (EG2+) only increased significantly in the subgroup without diagnosed viral infection and particularly in atopic rhinitics. T‐suppressor (CD8+) cells also increased significantly (median +178.3 cells mm2,P= 0.004). Epithelial expression of intercellular adhesion molecule‐1 (ICAM‐1) expression increased in four atopic rhinitics during colds. Bronchial washings showed a significant increase in neutrophils (GM 1.53‐fold [1.04,2.25],P= 0.02).ConclusionLower airway inflammation was present in atopic and non‐atopic normal subjects with colds. Atopic subjects differed in that they were less likely to have positive virological tests and were more likely to show activated eosinophilia in the lower airway, despite a sim

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00593.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY