Segmental Challenge Research Articles

Effects of Allergen Challenge on Airway Epithelial Cell Gene Expression

Allergen exposure induces the airway epithelium to produce chemoattractants, proallergic interleukins, matrix-modifying proteins, and proteins that influence the growth and activation state of airway structural cells. These proteins, in turn, contribute to the influx of inflammatory cells and changes in structure that characterize the asthmatic airway. To use the response of the airway epithelium to allergen to identify genes not previously associated with allergic responses, we compared gene expression in cytokeratin-positive cells before and after segmental allergen challenge. After challenge with concentrations of allergen in the clinically relevant range, 755 (6%) of the detectable sequences had geometric mean fold-changes in expression, with 95% confidence intervals that excluded unity. Using a prospectively defined conservative filtering algorithm, we identified 141 sequences as upregulated and eight as downregulated, with confirmation by conventional polymerase chain reaction in all 10 sequences studied. Using this approach, we identified asthma-associated sequences including interleukin (IL-)-3, IL-4, and IL-5 receptor subunits, the p65 component of nuclear factor-kappaB, and lipocortin. The genomic response of the human airway to concentrations of allergen in the clinically relevant range involves a greater number of genes than previously recognized, including many not previously associated with asthma that are differentially expressed after airway allergen exposure.

Role of 90K protein in asthma and T H2-type cytokine expression

The 90K protein (mac-2 binding protein) is a member of the macrophage scavenger receptor cysteine-rich domain superfamily. Although systemic levels of 90K protein have been correlated with inflammation in many diseases, its role in asthma is unknown. To determine whether asthma is associated with changes in the local and systemic expression of 90K protein and whether 90K protein affects the TH2 cytokine profile that is a hallmark of asthma. The 90K protein levels were measured in the systemic circulation of 69 individuals with asthma and 68 controls and in the bronchoalveolar lavage fluid of 9 controls and 7 atopic asthmatic patients before and after segmental allergen challenge. The effects of 90K protein on interleukin 4 (IL-4), IL-5, IL-13, and IL-6 production at protein and transcriptional levels in cultured human peripheral blood mononuclear cells were determined. Plasma concentrations of 90K protein were higher in asthmatic individuals vs controls (P = .002), were higher in the bronchoalveolar lavage fluid of asthmatic patients vs controls (P < .01), and increased after segmental allergen challenge in atopic asthmatic patients (P < .03). Increasing concentrations of 90K protein resulted in significantly reduced IL-4, IL-5, and IL-13 concentrations and increased IL-6 concentrations in the supernatants of cultured peripheral blood mononuclear cells (P < .05). Reverse transcriptase-polymerase chain reaction studies showed parallel changes in the transcription of these cytokines. Local and systemic concentrations of 90K protein are increased in asthma. Its inhibitory effect on TH2 cytokine transcription suggests that increased 90K protein expression is an attempt to limit the ongoing inflammation in asthma.

Interleukin-5 receptors on human lung eosinophils after segmental allergen challenge.

IL-5 is a specific cytokine for eosinophil accumulation, activation and prolongation of survival and can be recovered in elevated concentrations from the bronchoalveolar compartment in atopic asthma following allergen challenge. The action of IL-5 is mediated via the specific IL-5 receptor-alpha (IL-5Ralpha). Although in vitro data suggest that IL-5R expression is regulated by cytokines such as IL-3, IL-5 and GM-CSF, IL-5R regulation in vivo and its kinetics following allergen provocation are incompletely understood. We investigated IL-5R regulation in vivo following segmental allergen provocation (SAP) with an individually standardized dose of allergen in 12 patients with atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min and 42 h (eight patients) after allergen challenge. In addition to differential cell counts, IL-5Ralpha was measured by flow cytometry and IL-5 concentrations in bronchoalveolar lavage (BAL) fluid were determined by ELISA. IL-5Ralpha expression decreased significantly on peripheral blood and on BAL eosinophils 18 and 42 h after SAP. In contrast, IL-5 concentrations increased significantly in BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there were detectable IL-5 concentrations in serum 18 or 42 h after allergen exposure. Although there was no correlation between IL-5 concentrations and IL-5Ralpha expression on eosinophils in BAL, our data support previous in vitro and in vivo findings of a negative feedback mechanism between IL-5 concentrations and IL-5Ralpha expression on eosinophils.

CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge.

T-helper (Th) 2 cytokines are thought to mediate most features of allergic inflammation in atopic asthma. However, it remains unclear whether chemokine pathways direct selective recruitment of Th2 cells to the airways during human allergic responses. Bronchoalveolar lavage (BAL) was performed in 15 nonsmoking mild atopic asthmatics before and 24 h after a fibreoptic segmental allergen challenge, and chemokines related to T-cell recruitment were assayed by ELISA. The Th2-related C-C chemokine (CCR)4 ligands, macrophage-derived chemokine/C-C chemokine ligand (CCL)22 and thymus and activation-regulated chemokine/CCL17, were increased in BAL after challenge. These chemokines correlated significantly with lymphocyte numbers and with interleukin (IL)-5 and IL-13 in post-challenge BAL. In contrast, two out of three putative Th1-related chemokines did not change. There were no alterations in monokine induced by interferon (IFN)-gamma/CXC chemokine ligand (CXCL)9 or macrophage inflammatory protein-1alpha/CCL3; whereas a significant increase in IFN-induced protein-10kDa/CXCL10 was observed, which did not correlate with the T-cell influx. In peripheral mononuclear cells from atopic donors, CCL22 and CCL17 were induced by IL-4 and IL-13, further supporting the relationship between CCL22/CCL17 and Th2 cytokines. Finally, CCL22 was able to trigger actin polymerisation in peripheral CD4+ T-cells expressing CCR4. Thus, C-C chemokine receptor 4 ligands are up-regulated in the airways of atopic asthmatics following allergen exposure, contribute to the T-cell influx to the airways and are closely related to the Th2-cytokine response.

Allergens, Viruses, and Asthma Exacerbations

In adults and children with asthma, viral infections (rhinovirus [RV] infection being the most prevalent) will often trigger an increase in symptomatology. The mechanisms responsible for viral-induced exacerbations remain uncertain. Proposed mechanisms include direct infection of the lower respiratory tract, the inflammatory response to viruses, increases in bronchial responsiveness and up-regulation of intercellular adhesion molecule-1 expression in bronchial epithelium. In addition, exposure to allergens, especially seasonal allergens, in sensitized asthmatic individuals have been implicated in asthma attacks. Increased levels of exposure in sensitized asthmatics have been related to increases in hospital admissions and emergency room visits, increased bronchial hyperresponsiveness, increased levels of exhaled nitric oxide, lower levels of lung function, increased treatment requirements, and even increased mortality. In recent years studies have suggested that viruses and allergens may have a synergistic effect on individuals with asthma, thus having a greater influence on exacerbation rate together than either factor alone. Models of experimentally induced RV infection in both allergic and nonallergic individuals using bronchoalveolar lavage and segmental allergen challenge have helped researchers to investigate the possibility of an interaction between allergen sensitization, exposure, and virus infection and their role in the induction of an asthma exacerbation. This review aims to summarize the evidence supporting the role of viruses (in particular RV) as well as the role of, and interaction with, allergen sensitization and exposure on exacerbations of asthma.

Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, interleukin (IL)-4 and IL-13 after segmental allergen challenge and their effects on alpha-smooth muscle actin and collagen III synthesis by primary human lung fibroblasts.

Asthmatic airway remodelling is characterized by myofibroblast hyperplasia and subbasement membrane collagen deposition. We hypothesized that cytokines and growth factors implicated in asthmatic airway remodelling are increased in bronchoalveolar lavage (BAL) fluid of asthmatics after segmental allergen challenge (SAC), and that these growth factors and cytokines increase alpha-smooth muscle actin (alpha-SMA) and collagen III synthesis by human lung fibroblasts (HLFs). Transforming growth factor (TGF)-beta1, TGF-beta2, IL-4 and IL-13 levels were measured in BAL fluid from 10 asthmatics and 9 non-asthmatic controls at baseline and then 1 day, 1 week and 2 weeks after SAC. Confluent cultures of HLFs were stimulated by exogenous addition of TGF-beta1, TGF-beta2, IL-4 or IL-13 (concentration range 0.01-10 ng/mL) over 48 h. Collagen III was measured in culture supernates and alpha-SMA in cell lysates by Western blot. At baseline, there was no difference in BAL fluid concentrations of TGF-beta1, IL-4 and IL-13 between asthmatics and controls; however, non-asthmatics had higher concentrations of total TGF-beta2. In asthmatics, BAL fluid concentrations of all four factors increased significantly 1 day after SAC. TGF-beta1, TGF-beta2 and IL-13 concentrations returned to baseline by 1 week after SAC, but BAL fluid IL-4 concentration remained elevated for at least 2 weeks. TGF-beta1, TGF-beta2 and IL-4 significantly increased alpha-SMA in fibroblasts, but only IL-4 caused corresponding increases in collagen III synthesis. IL-13 had no direct effects on collagen III synthesis and alpha-SMA expression. Because IL-4 caused a dose-dependent increase in alpha-SMA and collagen III synthesis, it may be an important cytokine mediating asthmatic airway remodelling. TGF-beta1 and TGF-beta2 may also play a role in airway remodelling by stimulating phenotypic change of fibroblasts to myofibroblasts. Additionally, collagen III synthesis appears to be independent of myofibroblast phenotype and is apparently regulated by different growth factors and cytokines.

Human eosinophils express IL-18 mRNA and protein

Rationale The role and contribution of eosinophils to allergic inflammation is under re-evaluation and may include activities that regulate lymphocyte function. For example, recent studies in mice suggest that IL-18 regulates polarization of Th1 and Th2 lymphocytes and results in generation of IL-4 and IL-13 to cause airway dysfunction. We sought to determine whether human eosinophils are capable of producing IL-18 and thus participate in regulation of Th1 or Th2 lymphocytes. Methods Human peripheral blood eosinophils and bronchoalveolar lavage (BAL) eosinophils (obtained 24 hours post segmental antigen challenge) were isolated and then assayed for the expression of IL-18 mRNA and secreted IL-18 protein by quantitative real-time PCR and ELISA assays, respectively. Results Isolated peripheral blood eosinophils that were cultured for up to 24 hours were found to secrete IL-18, which was not modulated by IL-5 treatment. Quantitative real time PCR revealed that eosinophils purified from BAL also express IL-18 mRNA. ELISA analysis of the corresponding BAL fluid detected IL-18 protein with a mean concentration of 84 pg/mL in atopic individuals and 48 pg/mL in nonatopic controls. Conclusions We demonstrated that human eosinophils can express IL-18 mRNA and secrete IL-18 protein. Given that the precise role for eosinophils in the asthmatic lung airway is unclear, we propose that eosinophil secretion of cytokines, such as IL-18, may play a regulatory role in airway inflammation by modulation of Th1 or Th2 lymphocytes.

The CX 3C chemokine fractalkine in allergic asthma and rhinitis

Background Unlike other chemokines, fractalkine is expressed as a membrane-bound form, mainly on endothelial and epithelial cells, and can be shed as a soluble chemotactic form. Fractalkine can capture leukocytes expressing its receptor (CX 3CR 1), including T lymphocytes, rapidly and firmly in an integrin-independent manner. Because of its dual activity, fractalkine plays a major role in the transendothelial and transepithelial migration of leukocytes during inflammation. Objective We sought to study the fractalkine-CX 3CR 1 axis in patients with allergic airways diseases. Methods Plasma fractalkine levels were measured by means of ELISA in 19 control subjects and 55 patients with symptomatic allergic rhinitis, asthma, or both, and CX 3CR 1 function was studied by using triple-color flow cytometry in circulating T-lymphocyte subpopulations. Segmental allergen challenge was performed in 16 allergic asthmatic patients to analyze fractalkine expression and inflammatory cell recruitment in bronchoalveolar lavage fluid and bronchial biopsy specimens. Results Compared with control subjects, patients with symptomatic allergic rhinitis and asthmatic patients had increased circulating fractalkine levels, and CX 3CR 1 function was upregulated in circulating CD4 + T lymphocytes. Twenty-four hours after segmental allergen challenge, bronchoalveolar lavage fluid soluble fractalkine concentrations increased and correlated with the total number of recruited cells. Bronchial epithelial and endothelial cells expressed high levels of the membrane-bound form of fractalkine before and after challenge. Conclusion Allergic asthma and rhinitis are associated with systemic and bronchial upregulation of the chemotactic axis fractalkine-CX 3CR 1. This might contribute to the rapid recruitment of circulating CD4 + T lymphocytes in the airways after allergen stimulation.

Natural porcine surfactant augments airway inflammation after allergen challenge in patients with asthma.

There is increasing evidence for a role of pulmonary surfactant in asthma and allergic inflammation. In murine asthma models, recent studies have demonstrated that surfactant components downregulate the allergic inflammation. Therefore, we tested the hypothesis that in individuals with mild asthma, a natural porcine surfactant preparation (Curosurf) given before segmental allergen challenge can reduce the allergic airway inflammation. Ten patients with asthma and five healthy control subjects were treated in two segments with either Curosurf or vehicle followed by local allergen challenge. Six additional patients with asthma received Curosurf before allergen challenge in one segment as above, but the second segment was instilled with Curosurf without allergen challenge. Unexpectedly, surfactant treatment augmented the eosinophilic inflammation 24 hours after allergen challenge. A direct chemotactic effect of Curosurf was excluded. However, levels of eotaxin and interleukin-5 were increased in bronchoalveolar lavage after Curosurf treatment, whereas IFN-gamma-levels and numbers of IFN-gamma(+) T cells were decreased. Curosurf had no influence on spreading and retention of allergen determined by allergen uptake in mice. These findings demonstrate that treatment with a natural porcine surfactant results in an augmentation of the eosinophilic inflammation after allergen challenge that is more likely due to immunomodulatory effects than to biophysical properties of the surfactant.

Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions

Background Segmental antigen bronchoprovocation has long been used as a model to study allergic pulmonary inflammatory responses. Among the characteristics of the resulting cellular infiltrate is the preferential recruitment of T H 2 lymphocytes. The mechanisms responsible for their selective recruitment remain unknown, but T H 2 cells preferentially express the chemokine receptors CCR4 and CCR8. Objectives We tested the hypothesis that the chemokines thymus- and activation-regulated chemokine (TARC) (CCL17) and macrophage-derived chemokine (MDC) (CCL22), whose receptor is CCR4, and I-309 (CCL1), whose receptor is CCR8, would be released at sites of segmental allergen challenge. Methods Segmental allergen challenge with saline or allergen was performed in 10 adult allergic subjects with asthma, who were off medications. Bronchoalveolar lavage (BAL) was performed at both the saline- and allergen-challenged sites 20 hours after challenge. BAL fluids were analyzed for total cell counts and differentials, and supernatants were assayed by ELISA for levels of TARC, MDC, and I-309. As a control, the BAL fluids were also analyzed for levels of interferon-inducible protein 10 (IP-10) (CXCL10), an IFN-γ—induced chemokine active on CXCR3, a chemokine receptor that is preferentially expressed on T H1 lymphocytes. Results Allergen challenge led to an approximately 6-fold increase in total leukocytes, including lymphocytes, compared with those seen at saline-challenged sites. At antigen-challenged sites, eosinophils predominated. Chemokine levels at control, saline-challenged sites were either below the detectable limit or low, with the predominant chemokine detected being IP-10. At antigen-challenged sites, levels of MDC, TARC, and IP-10 were all significantly increased compared with saline sites, each with a median of 486 to 1130 pg/mL detected. On the basis of a comparison with serum values, BAL chemokine levels at most antigen-challenged sites could not be accounted for by transudation from plasma. In contrast, levels of I-309 were extremely low or undetectable in all BAL and serum samples tested. Finally, BAL levels of MDC significantly correlated with those for TARC, but no significant correlations were found between levels of chemokine and any cell type. Conclusions These data suggest that among the chemokines measured in this study, IP-10 is the predominant chemokine detected 20 hours after saline challenge, likely representing baseline production of a chemokine that favors T H 1 cell recruitment. At antigen-challenged sites, levels of both CCR4 and CXCR3 active chemokines, but not CCR8 active chemokines, are markedly increased and are produced at levels that are likely to have biologic significance. Given the preferential accumulation of T H 2 cells at these antigen-challenged sites, the increased production of CCR4-active chemokines might contribute to this response.

Chemokine receptor expression on human eosinophils from peripheral blood and bronchoalveolar lavage fluid after segmental antigen challenge

Background The recruitment of circulating eosinophils to the lung is a characteristic feature of allergic airway inflammation. Chemokine receptors likely play a role in this complex process. However, reports of chemokine receptor expression on human eosinophils are conflicting. Objective The aim of this study was to determine whether the chemokine receptor profile of human eosinophils change when these cells are recruited to the airway after an antigen challenge and development of an allergic inflammatory response. Methods Blood and bronchoalveolar lavage (BAL) cells were obtained from 13 allergic subjects 48 hours after segmental bronchoprovocation with antigen. The CC chemokine receptor (CCR) 1 to 7, 9, and CXC chemokine receptor (CXCR) 1 to 4 were determined by flow cytometric analysis of whole blood and unseparated BAL cells. Results Compared with their circulating counterparts, airway eosinophils had decreased CCR3 and increased CCR4, CCR9, and CXCR3 expression on their cell surface. Furthermore, expression of CCR3, CCR4, and CXCR3 was significantly correlated with the percentage of eosinophils in BAL fluid at 48 hours. Eosinophils also expressed CXCR4, but this receptor did not change after antigen-induced recruitment to the airway. In contrast, the expression of CCR1, CCR2, CCR5, CCR6, CCR7, CXCR1, and CXCR2 remained undetectable on either blood or BAL eosinophils. Conclusions Our data suggest that recruitment of eosinophils to the airway is associated with a modulation of their chemokine receptor profiles. These changes in chemokine receptors could be involved in determining eosinophil function and antigen-induced airway inflammation.

Recruitment of antigen-specific Th1-like responses to the human lung following bronchoscopic segmental challenge with purified protein derivative of Mycobacterium tuberculosis.

Although the mechanisms of specific immunity to Mycobacterium tuberculosis in humans are poorly understood, responses of Th1-like CD4+ T cells appear to be essential for protection. We hypothesized that healthy individuals displaying positive skin-test responses to purified protein derivative of M. tuberculosis (PPD) would have the capacity to mobilize M. tuberculosis-specific Th1 cells to the lung in response to bronchoscopic challenge with PPD. Local instillation of 0.5 tuberculin units of PPD was followed 48 h subsequently by bronchoalveolar lavage (BAL) of PPD-challenged and control segments. In PPD-positive subjects, PPD challenge resulted in a 2.7-fold increase in total BAL cells and in an increase in the percentage of lymphocytes in BAL from 10 to 19%. The BAL lymphocytosis observed in PPD-challenged segments was characterized by an increased percentage of CD4+ T cells and by increased numbers of cells capable of antigen-specific interferon-gamma production. In contrast, PPD-negative subjects did not develop local inflammation following PPD challenge. These findings indicate that bronchoscopic challenge with PPD results in recruitment of antigen-specific recall responses to the lung. This novel approach may be useful in clarifying the basis of local immunity against M. tuberculosis, and could serve more generally as a model of the development of Th1-like responses in the human lung.

Segmental allergen challenge in patients with atopic asthma leads to increased IL-9 expression in bronchoalveolar lavage fluid lymphocytes

Background: IL-9 is a TH2 cell-derived cytokine that might be involved in the pathophysiology of allergic diseases. Little is known about its expression and release during the allergic response in the human lung. Objective: The expression of IL-9 was measured in 10 atopic subjects with mild asthma and 5 nonatopic healthy control subjects at baseline and 24 hours after segmental sham and allergen challenge. Methods: IL-9 protein was measured in bronchoalveolar lavage (BAL) fluid by means of ELISA and detected within the BAL cells by means of immunocytochemistry. Furthermore, IL9 mRNA expression of BAL cells was detected by means of real-time PCR. Results: Although only low or undetectable amounts of IL9 mRNA and IL-9 protein were present in nonatopic control subjects and atopic asthmatic patients at baseline, there was an increase after segmental allergen challenge in the atopic subjects. Lymphocytes were identified as major cellular sources of IL-9 production by means of immunocytochemistry. Furthermore, IL-9 protein and IL9 mRNA expression correlated with eosinophil numbers in BAL fluid. Conclusions: These findings demonstrate that IL-9 is specifically upregulated after local allergen challenge in the lungs of atopic asthmatic patients. Lymphocytes are the major cellular source of IL-9. The increased expression and its correlation with eosinophil numbers suggest a potential role for IL-9 in the late phase of the allergic response. (J Allergy Clin Immunol 2003;111:1319-27.)

Local release of eosinophil peroxidase following segmental allergen provocation in asthma.

Eosinophil peroxidase (EPO) is an eosinophilic basic protein, which leads to increased permeability and damage of bronchial epithelial cells in asthma. As little is known about its local expression and release in humans the intracellular expression in lung and peripheral eosinophils and the concentrations of EPO in bronchoalveolar lavage (BAL) fluid and serum was investigated in patients with asthma. Twelve mild atopic asthmatic and nine control subjects underwent segmental sham and allergen challenge. EPO concentrations in BAL fluid and serum were determined by immunoassay and flow cytometry was used to determine the intracellular expression of EPO in BAL-derived and peripheral eosinophils. In asthmatic patients a large increase in BAL eosinophils--total cells: median 9.5 x 10(6) (range: 0.5 to 455.0 x 10(6)); relative: 38% (1 to 91%)--was detectable 24 h following allergen challenge, but peripheral blood eosinophil counts did not change. Concentrations of EPO in BAL fluid increased from 1 microg/L (1.0 to 6.8 microg/L) to 42 microg/L (5.6 to 379.6 microg/L; P < 0.01) after allergen but not after saline challenge (1.5 microg/L; 1.0 to 21.9 microg/L), whereas in control subjects all measurements were below the detection limit. Serum concentrations of EPO increased slightly from 18.3 microg/L (3.0 to 56.8 microg/L) to 27 microg/L (3.8 to 133.9 microg/L; P < 0.05) 24 h after allergen challenge in asthmatic patients. Furthermore, the intracellular expression of EPO (measured as mean fluorescence intensity) was decreased in BAL eosinophils compared with blood eosinophils (mean fluorescence intensity 29 (7 to 71) vs. 48 (20 to 85); P < 0.01) after allergen challenge. The finding of increased EPO concentrations in the BAL fluid and decreased intracellular EPO expression in pulmonary eosinophils of asthmatic patients reflects the allergen-triggered release of EPO into the bronchial space.

Mechanisms of asthma

Airway inflammation is a key factor in the mechanisms of asthma. Articles published in the Journal of Allergy and Clinical Immunology this past year have highlighted the utility of investigative bronchoscopy with segmental antigen challenge and induced sputum analyses to evaluate features of airway inflammation in relationship to asthma severity. Peripheral blood cell generation of cytokines IFN-γ (TH1) and IL-5 (TH2) was used to evaluate the relationship of the balance of TH1/TH2 cytokines to asthma persistence and severity in a 42-year, longitudinal study. Chemokines, including thymus and activation-regulated chemokine, are important to the regulation of inflammation and IgE synthesis. Their potential role in asthma has also been evaluated. Finally, albuterol (R)- and (S)-enantiomers may have distinct effects on airway relaxation and regulation of inflammation, suggesting the possibility that monoisomeric therapy has therapeutic advantages. The potential contribution of genetic factors and mechanisms to airway inflammation and remodeling also continues to be an area of intense investigation. During the past year a number of articles published in the Journal of Allergy and Clinical Immunology have identified and clarified potential genetic mechanisms in asthma. The contribution of genetics to asthma has been examined in a wide variety of studies, ranging from epidemiologic association and twin studies all the way to molecular analysis through microarray gene expression experiments. (J Allergy Clin Immunol 2003;111:S799-804.)

Modulation of Vasodilator-Stimulated Phosphoprotein In Vivo in Human Epithelial Cells by Segmental Allergen Challenge and β2-Agonist Therapy

The attachment and migration of airway epithelial cells is an important aspect of the repair of antigen-induced inflammatory injury in patients with asthma. Cytoskeletal reorganization is required for the altered attachment and migration of epithelial cells. Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion and actin filament binding in a variety of cells and acts as an inhibitor of cell movement. Phosphorylation of VASP via cyclic adenosine monophosphate-dependent and cyclic guanosine monophosphate-dependent protein kinases releases this “brake” on cell motility.

Increased Messenger RNA Expression of c-maf and GATA-3 After Segmental Allergen Challenge in Allergic Asthmatics

Increased Messenger RNA Expression of c-maf and GATA-3 After Segmental Allergen Challenge in Allergic Asthmatics

Increased Expression of Interleukin-9 Messenger RNA After Segmental Allergen Challenge in Allergic Asthmatics

2003;123;370S-371S Chest Andreas Hagenberg, Armin Braun and Norbert Krug Veit J. Erpenbeck, Jens M. Hohlfeld, Marc Discher, Harald Krentel, * Challenge in Allergic Asthmatics c-maf and GATA-3 After Segmental Allergen Increased Messenger RNA Expression of http://chestjournal.chestpubs.org/content/123/3_suppl/370S.2.full.html services can be found online on the World Wide Web at: The online version of this article, along with updated information and ISSN:0012-3692 ) http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ( written permission of the copyright holder. this article or PDF may be reproduced or distributed without the prior Dundee Road, Northbrook, IL 60062. All rights reserved. No part of Copyright2003by the American College of Chest Physicians, 3300 Physicians. It has been published monthly since 1935. is the official journal of the American College of Chest Chest

Concentration of Cytokines and Growth Factors in BAL Fluid After Allergen Challenge in Asthmatics and Their Effect on α-Smooth Muscle Actin and Collagen III Synthesis by Human Lung Fibroblasts

Asthma is characterized histologically by bronchial subepithelial fibrosis and increased numbers of myofibroblasts. It has been proposed that these myofibroblasts are responsible for the characteristic subepithelial collagen deposition seen in asthma. We hypothesized that the concentration of growth factors and cytokines that is important in asthmatic airway remodeling are elevated in BAL fluid after segmental antigen challenge (SAC). We further hypothesized that these growth factors and cytokines increase α-smooth muscle actin (SMA) and collagen III synthesis by human lung fibroblasts (HLFs).

Chemokine receptor expression on lung-derived T cells of mild asthmatics after segmental allergen challenge

Chemokine receptor expression on lung-derived T cells of mild asthmatics after segmental allergen challenge