Home About us Contact
|
Home About us Contact | ||
|
|
||
Allergic Airway Inflammation (allergic + airway_inflammation)
Selected AbstractsEffects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2005I. Machida Summary Background Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. ,2 -agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. Objectives To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. Methods Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. Results Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in ,2 -agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. Conclusions Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting ,2 -agonists do not modify DCs-induced allergic airway inflammation. [source] Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airwaysCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2005Q. T. Dinh Summary Background Allergic airway inflammation has been shown to induce pro-inflammatory neuropeptides such as tachykinin peptides substance P (SP) and neurokinin A (NKA) together with related peptide like calcitonin gene-related peptide (CGRP) in nodose sensory neurons innervating guinea-pig airways. Objective The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular,nodose ganglion neurons innervating the murine airways. Methods Using retrograde neuronal tracing technique in combination with double-labelling immunohistochemistry, the expression of SP/NKA was investigated in a murine model of allergic airway inflammation. Results Allergic airway inflammation was found to induce the expression of SP/NKA (13.2±1.43% vs. 5.8±0.37%, P<0.01) in large-diameter (>20 ,m) vagal sensory neurons retrograde labelled with Fast blue dye from the main stem bronchi. Conclusion Based on the induction of tachykinins in airway-specific large-sized jugular,nodose ganglia neurons by allergic airway inflammation, the present study suggests that allergen sensitization and challenge may lead to de novo induction of tachykinins in neurons. This may partly contribute to the pathogenesis of airways diseases such as allergic airway inflammation. [source] Allergic airway inflammation is exacerbated during acute influenza infection and correlates with increased allergen presentation and recruitment of allergen-specific T-helper type 2 cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2004B. J. Marsland Summary Background Respiratory viral infections are a leading cause of the hospitalization of asthmatics, however, the cellular immunological interactions which underlie these two diseases remain elusive. Objective We sought to characterize the effect influenza viral infection has on allergic airway inflammation and to identify the cellular pathways involved. Methods We have used an ovalbumin (OVA) model of allergic airway inflammation, which involves sensitization of animals with OVA adsorbed in alum adjuvant followed by an intranasal challenge with OVA in phosphate-buffered saline. To study T cell recruitment into the lung, we adoptively transferred in vitro activated T cell receptor-transgenic T cells, which were subsequently identified by fluorescence-activated cell sorting (FACS) analysis. In addition, to study in vivo dendritic cell (DC) migration, we administered fluorescently labelled dextran and identified DCs that had phagocytosed it by FACS analysis. Results We found that different stages of influenza infection had contrasting effects upon the outcome of OVA-induced allergic airway inflammation. The allergic response against OVA was exacerbated during the acute stage of influenza infection; however, mice were protected against the development of airway eosinophilia at late time-points following infection. We investigated the mechanisms responsible for the virus-induced exacerbation and found that the response was partially independent of IL-4 and that there was increased delivery of inhaled allergens to the draining lymph node during the acute stage of the infection. In addition, virus-induced inflammation in the lung and draining lymph node resulted in the non-specific recruitment of circulating allergen-specific effector/memory cells. Conclusion In addition to virus-mediated damage to the lung and airways, influenza viral infection can also enhance unrelated local allergic responses. [source] T-bet expression by dendritic cells is required for the repolarization of allergic airway inflammation,EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2008Karin L. Heckman Abstract By cross-linking B7-DC on dendritic cells (DC) the human IgM antibody (B7-DC XAb) shifts polarized immune responses from Th2 to Th1 in an antigen-specific manner. The molecular determinants governing the ability of DC to reprogram the polarity of T cell recall responses are not yet known. In addition to the expected role of T-bet expressed by T cells in regulating Th1 responses, we find using in vitro assays and an established in vivo model of allergic airway inflammation that T-bet expression by DC is also required for the polarity shift promoted by B7-DC XAb. T-bet expression by both T cells and DC is critically important for B7-DC XAb-induced down-regulation of IL-4, up-regulation of IFN-, and suppression of allergic airway inflammation. Moreover, retroviral reconstitution of T-bet expression in T-bet-deficient DC rescued their ability to modulate both naive and memory T-cell responses from Th2 to Th1. Our observations further our understanding of the critical mediators controlling the ability of DC to modify the responses of previously activated T cells and reveal the interesting use of the same transcription factor to regulate the inductive phenotype of DC and the inducible phenotype of T cells. [source] Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCGIMMUNOLOGY, Issue 1pt2 2009Hai-Feng Ou-Yang Summary Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette,Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-, (IFN-,) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4+ CD25+ Foxp3+ T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4+ CD25+ T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-, (TGF-,)-producing CD4+ CD25+ Foxp3+ regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma. [source] Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthmaIMMUNOLOGY, Issue 2 2006Marian L. Kruzel Summary Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidases and in contact with mucosal surfaces generate superoxide anion (O2,,). In the presence of iron, O2,, may be converted to more reactive oxygen radicals, such as to H2O2 and/or ,OH, which may augment antigen-induced airway inflammation. The aim of the study was to examine the impact of lactoferrin (LF), an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial cells and accumulation of inflammatory and mucin-producing cells in airways in a mouse model of allergic airway inflammation. Results show that LF lowered RWE-induced increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. Most importantly, LF significantly decreased accumulation of eosinophils into airways and subepithelium of intranasally challenged, sensitized mice. LF also prevented development of mucin-producing cells. Amb a 1, the major allergenic ragweed pollen antigen lacking NAD(P)H oxidase activity, induced low-grade airway inflammation. When administered along with glucose oxidase (G-ox), a superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which was significantly lowered by LF. Surprisingly, LF decreased also inflammation caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced inflammation. We postulate that free iron in the airways chemically reduces O2,, to more reactive species which augment antigen-induced inflammation in a mouse model of asthma. Our results suggest the utility of LF in human allergic inflammatory disorders. [source] Piperine inhibits eosinophil infiltration and airway hyperresponsiveness by suppressing T cell activity and Th2 cytokine production in the ovalbumin-induced asthma modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009Seung-Hyung Kim Abstract Objectives This study aimed to investigate the effect of piperine on airway hyper-responsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, immunoglobulin E and histamine production in a murine model of asthma. Methods Asthma was induced in Balb/c mice by ovalbumin sensitization and inhalation. Piperine (4.5 and 2.25 mg/kg) was orally administered 5 times a week for 8 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was determined and samples of bronchoalveolar lavage fluid, lung cells and serum were collected for further analysis. Key findings Piperine-treated groups had suppressed eosinophil infiltration, allergic airway inflammation and airway hyperresponsiveness, and these occurred by suppression of the production of interleukin-4, interleukin-5, immunoglobulin E and histamine. Moreover, polymerase chain reaction products for thymus and activation regulated chemokine from lung cell RNA preparations were decreased in the piperine-treated group compared with control groups, although transforming growth factor-, products were increased in the piperine-treated group. Conclusions The results suggest that the therapeutic mechanism by which piperine effectively treats asthma is based on a reduction of Th2 cytokines (interleukin-4, interleukin-5), eosinophil infiltration, and by marked reduction of thymus and activation regulated chemokine, eotaxin-2 and interleukin-13 mRNA expression (especially transcription of nuclear factor-, dependent genes) in lung tissue, as well as reduced interleukin-4, interleukin-5 and eotaxin levels in bronchoalveolar lavage fluid, and histamine and ovalbumin-specific immunoglobulin E production in serum. [source] Effect of natural seasonal pollen exposure and repeated nasal allergen provocations on elevation of exhaled nitric oxideALLERGY, Issue 11 2009K. Bergmann-Hug Background:, Exhaled nitric oxide (FENO) is a marker for allergic airway inflammation. We wondered whether in patients with intermittent allergic rhinitis only (i) natural pollen exposure and (ii) artificial pollen exposure by repeated nasal allergen provocations may lead to an elevation of FENO. Methods:, In two prospective studies, we compared the FENO of nonatopic controls with the FENO of nonasthmatic individuals with mild intermittent rhinitis to tree and/or grass pollen. Study I: 13 atopic individuals and seven controls had measurements of FENO, blood eosinophils and eosinophilic cationic protein (ECP) before, during and after pollen season. Study II: 16 atopic individuals and 12 controls had nasal allergen provocations on four following days out of pollen season, with daily measurements of FENO before, 2 and 6 h after provocation, and determination of blood eosinophils, ECP and FEV1 at baseline, on days 5 and 10,12. Results:, Natural pollen exposure (study I) caused a significant elevation of FENO in allergic individuals. Nasal allergen provocations (study II) did not elicit a statistically significant rise neither of FENO nor of blood eosinophils between baseline and day 5. However, a subgroup of four individuals with a rise of blood eosinophils during nasal allergen provocations showed also a rise of FENO. Conclusions:, We suppose that in allergic rhinitis a concomitant reaction of the bronchial system is dependent on a strong local inflammation leading to a generalized immune stimulation. [source] Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory airwaysALLERGY, Issue 3 2009S. O. Odemuyiwa Background:, Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan catabolism, is important in generating tolerance at the foetal,maternal interface. Studies using 1-methyl-tryptophan (1-MT), the specific inhibitor of IDO, showed that this enzyme is important in interferon-gamma (IFN-,)-dependent inhibition of allergic inflammation in the respiratory airway during immunotherapy. Aims of study:, We investigated the role of IDO in the development of allergic sensitization, leading to allergic inflammation and airway hyper-responsiveness (AHR). Methods:, We used a mouse model to generate mucosal tolerance to lipopolysaccharide-free ovalbumin (OVA) following repeated intranasal inoculation of OVA over a 3-day period. We tested the successful induction of tolerance by subsequent intraperitoneal (i.p.) sensitization followed by intranasal challenge with OVA. A slow-release pellet of 1-MT implanted into mice was used to block IDO activity prior to repeated intranasal inoculation of OVA. We measured T-cell proliferation in response to OVA, determined airway inflammation, and measured AHR to intranasal methacholine to investigate the role of IDO in sensitization to OVA. Results:, Repeated intranasal administration of OVA generated tolerance and prevented a subsequent sensitization to OVA via the i.p. route. This response was inhibited in mice receiving a slow-release pellet of 1-MT. However, we successfully reconstituted tolerance in mice receiving 1-MT following intra-peritoneal injection of a mixture of kynurenine and hydroxyanthranilic acid. Conclusion:, Our data suggest that, in addition to their role in IFN-,-mediated inhibition of allergic airway inflammation, products of tryptophan catabolism play an important role in the prevention of sensitization to potential allergens in the respiratory airway. [source] Mechanisms of virus-induced asthma exacerbations: state-of-the-art.ALLERGY, Issue 5 2007A GA2LEN, InterAirways document Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research. [source] REVIEW ARTICLE: Maternal Transmission of Asthma RiskAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Robert H. Lim Maternal asthma significantly increases the risk of asthma in offspring, but the mechanisms remain poorly defined. We review animal models used to study the maternal effect, focusing on a murine model developed in our laboratory. Mother mice rendered allergic to ovalbumin produce offspring that are more susceptible to allergic sensitization, seen as airway hyperresponsiveness and allergic airway inflammation after a sensitization protocol, which has minimal effects on newborns from normal mothers. Mechanistic analyses identify a role for interleukin-4 (based on pre-mating injection of neutralizing antibodies), dendritic cells and allergen-specific T cells (based on adoptive transfer experiments). Other maternal exposures (e.g. pollutant exposure and non-pulmonary allergy) can increase asthma susceptibility in offspring. This observation implies that the maternal transmission of asthma represents a final common pathway to various types of inflammatory stimuli. Identification of the shared molecular mechanisms in these models may allow better prevention and therapy. Current knowledge, gaps in knowledge and future directions are discussed. [source] Comparison of adjuvant and adjuvant-free murine experimental asthma modelsCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2009M. L. Conrad Summary Introduction The most widely used protocol for the induction of experimental allergic airway inflammation in mice involves sensitization by intraperitoneal (i.p.) injections of the antigen ovalbumin (OVA) used in conjunction with the adjuvant aluminium hydroxide (alum). Although adjuvants are frequently used, there are questions regarding the necessity of alum for murine asthma studies due to the non-physiological nature of this chemical. Objective The objective of this study was to compare experimental asthma phenotypes between adjuvant and adjuvant-free protocols of murine allergic airway inflammation in an attempt to develop a standardized alternative to adjuvant use. Method An adjuvant-free OVA model of experimental asthma was investigated in BALB/c mice using i.p. or subcutaneous (s.c.) sensitization routes. For the s.c. sensitization, ,-galactosidase (,-gal) was also tested as an antigen. In addition, OVA adjuvant and adjuvant-free sensitization protocols were compared in BALB/c and C57BL/6 mice. Open-field testing was performed to assess the effect of alum on mouse behaviour. Results Comparison of adjuvant vs. adjuvant-free and i.p. vs. s.c. protocols revealed that both adjuvant use and route of antigen application significantly influenced OVA-specific antibody production. Comparison of adjuvant and adjuvant-free protocols in this study clearly demonstrated the non-requirement of alum for the induction of acute allergic airway inflammation, as both protocols induce a similar disease phenotype. BALB/c mice were significantly more susceptible than C57BL/6 mice to sensitization. Using the improved s.c. adjuvant-free protocol, it was demonstrated that alternative antigens such as ,-gal can also be utilized. Behavioural studies indicated severe distress in mice treated with alum. Conclusion The OVA s.c. adjuvant-free protocol used in this study generates a phenotype comparable to the benchmark adjuvant protocol widely used in the literature. The adjuvant-free alternative avoids the added complication of non-physiological adjuvants that may interfere with asthma treatment or prevention strategies. [source] Neurokinin-1 receptor activation induces reactive oxygen species and epithelial damage in allergic airway inflammationCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2007J. Springer Summary Background An induction of reactive oxygen species (ROS) is characteristic for inflammation but the exact pathways have not been identified for allergic airway diseases so far. Objective The aim of this study was to characterize the role of the tachykinin NK-1 receptor on ROS production during allergen challenge and subsequent inflammation and remodelling. Methods Precision-cut lung slices of ovalbumin (OVA)-sensitized mice were cultivated and ROS-generation in response to OVA challenge (10 ,g/mL) was examined by the 2,,7,-dichloroflourescein-diacetate method. Long-term ROS effects on epithelial proliferation were investigated by 5-bromo-2,-deoxyuridine incorporation (72 h). In vivo, the results were validated in OVA-sensitized animals which were treated intra-nasally with either placebo, the tachykinin neurokinin 1 (NK-1) receptor antagonist SR 140333 or the anti-oxidant N -acetylcystein (NAC) before allergen challenge. Inflammatory infiltration and remodelling were assessed 48 h after allergen challenge. Results ROS generation was increased by 3.7-fold, which was inhibited by SR 140333. [Sar9,Met11(O2)]-Substance P (5 nm) caused a tachykinin NK-1 receptor-dependent fourfold increase in ROS generation. Epithelial proliferation was decreased by 68% by incubation with [Sar9,Met11(O2)]-SP over 72 h. In-vivo, treatment with SR 140333 and NAC reduced epithelial damage (91.4% and 76.8% vs. placebo, respectively, P<0.01) and goblet cell hyperplasia (67.4% and 50.1% vs. placebo, respectively, P<0.05), and decreased inflammatory cell influx (65.3% and 45.3% vs. placebo, respectively, P<0.01). Conclusion Allergen challenge induces ROS in a tachykinin NK-1 receptor-dependent manner. Inhibition of the tachykinin NK-1 receptor reduces epithelial damage and subsequent remodelling in vivo. Therefore, patients may possibly benefit from treatment regime that includes radical scavengers or tachykinin NK-1 receptor antagonists. [source] Effects of 4 months of smoking in mice with ovalbumin-induced airway inflammationCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2007B. N. Melgert Summary Background The effects of smoking on asthma pathogenesis are complex and not well studied. We have shown recently that 3 weeks of smoking attenuates ovalbumin (OVA)-induced airway inflammation in mice and that 4,6 months of smoking induces emphysema in mice without airway inflammation. Effects of combined long-term smoking and OVA exposure have not been investigated so far. Objective To study whether long-term smoking affects progression of allergic airway inflammation and/or enhances the development of emphysema in mice. Methods Mice were sensitized to OVA and challenged with saline or OVA aerosols for 6 months. From 2 months onwards, mice were also exposed to air or smoke. Lung tissue was analysed for extent of inflammation, emphysema, remodelling and for cytokine levels, and serum for OVA-specific IgE levels. Results Chronic OVA exposure of 6 months resulted in a T helper type 2 (Th2)-type inflammation with increased levels of IL-4, IL-5, IL-6 and infiltration of eosinophils, CD4+ T cells, macrophages and plasma cells. Smoking induced a Th17-type of airway inflammation, characterized by neutrophils, macrophages, B cells and increased levels of IL-17, IL-6, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1. Concomittant smoking and OVA exposure resulted in inflammation similar to OVA exposure alone. OVA exposure increased IgE levels compared with saline exposure, and smoking did not further increase these levels. Conclusion We did not find evidence for increased inflammation, IgE levels or emphysema in mice with allergic airway inflammation after 4 months of smoking compared with non-smoking. However, a 4-month exposure to smoke alone did enhance neutrophilic airway inflammation characterized by high pulmonary IL-17 levels. A Th2 inflammatory environment due to OVA exposure may be one explanation as to why no further detrimental effects of smoking on allergic airway inflammation were found. [source] Effects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2005I. Machida Summary Background Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. ,2 -agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. Objectives To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. Methods Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. Results Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in ,2 -agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. Conclusions Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting ,2 -agonists do not modify DCs-induced allergic airway inflammation. [source] Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airwaysCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2005Q. T. Dinh Summary Background Allergic airway inflammation has been shown to induce pro-inflammatory neuropeptides such as tachykinin peptides substance P (SP) and neurokinin A (NKA) together with related peptide like calcitonin gene-related peptide (CGRP) in nodose sensory neurons innervating guinea-pig airways. Objective The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular,nodose ganglion neurons innervating the murine airways. Methods Using retrograde neuronal tracing technique in combination with double-labelling immunohistochemistry, the expression of SP/NKA was investigated in a murine model of allergic airway inflammation. Results Allergic airway inflammation was found to induce the expression of SP/NKA (13.2±1.43% vs. 5.8±0.37%, P<0.01) in large-diameter (>20 ,m) vagal sensory neurons retrograde labelled with Fast blue dye from the main stem bronchi. Conclusion Based on the induction of tachykinins in airway-specific large-sized jugular,nodose ganglia neurons by allergic airway inflammation, the present study suggests that allergen sensitization and challenge may lead to de novo induction of tachykinins in neurons. This may partly contribute to the pathogenesis of airways diseases such as allergic airway inflammation. [source] Unravelling synergistic immune interactions between respiratory virus infections and allergic airway inflammationCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2004J. Schwarze No abstract is available for this article. [source] Allergic airway inflammation is exacerbated during acute influenza infection and correlates with increased allergen presentation and recruitment of allergen-specific T-helper type 2 cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2004B. J. Marsland Summary Background Respiratory viral infections are a leading cause of the hospitalization of asthmatics, however, the cellular immunological interactions which underlie these two diseases remain elusive. Objective We sought to characterize the effect influenza viral infection has on allergic airway inflammation and to identify the cellular pathways involved. Methods We have used an ovalbumin (OVA) model of allergic airway inflammation, which involves sensitization of animals with OVA adsorbed in alum adjuvant followed by an intranasal challenge with OVA in phosphate-buffered saline. To study T cell recruitment into the lung, we adoptively transferred in vitro activated T cell receptor-transgenic T cells, which were subsequently identified by fluorescence-activated cell sorting (FACS) analysis. In addition, to study in vivo dendritic cell (DC) migration, we administered fluorescently labelled dextran and identified DCs that had phagocytosed it by FACS analysis. Results We found that different stages of influenza infection had contrasting effects upon the outcome of OVA-induced allergic airway inflammation. The allergic response against OVA was exacerbated during the acute stage of influenza infection; however, mice were protected against the development of airway eosinophilia at late time-points following infection. We investigated the mechanisms responsible for the virus-induced exacerbation and found that the response was partially independent of IL-4 and that there was increased delivery of inhaled allergens to the draining lymph node during the acute stage of the infection. In addition, virus-induced inflammation in the lung and draining lymph node resulted in the non-specific recruitment of circulating allergen-specific effector/memory cells. Conclusion In addition to virus-mediated damage to the lung and airways, influenza viral infection can also enhance unrelated local allergic responses. [source] Expression and function of the ST2 gene in a murine model of allergic airway inflammationCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2002K. Oshikawa Summary Background We have recently reported that soluble ST2 protein levels are elevated in the sera of patients with asthma, and correlate well with the severity of asthma exacerbation. However, the role, function, and kinetics of soluble ST2 expression in asthma remain unclear. Objective The objective of the present study was to clarify the function and kinetics of soluble murine (m) ST2 expression in a murine asthma model. Methods We analyzed the kinetics of gene and protein expression of mST2 in sera or lung tissue after allergen (ovalbumin; OVA) challenge in a murine model of allergic airway inflammation, the effects of mST2 protein on OVA-induced Th2 cytokine production in vitro from splenocytes of sensitized mice, and the effects of soluble mST2 on Th2-dependent allergic airway inflammation by in vivo gene transfer of mST2. Results Serum mST2 protein levels increased to the maximal level 3 h after the allergen challenge, before serum IL-5 levels peaked. The mRNA expression of mST2 in lung tissue was induced after the allergen challenge, while that in the spleen was constitutively detected. Furthermore, pre-treatment with mST2 protein significantly inhibited the production of IL-4 and IL-5, but not IFN-,, from OVA-stimulated splenocytes in vitro, and intravenous mST2 gene transfer resulted in a drastic reduction in the number of eosinophils and in the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid, compared with those in response to transfer of non-coding plasmid vector or of lipid alone. Conclusion These results suggest that increases in endogenous mST2 protein after allergen exposure may modulate Th2-mediated airway inflammation, and that in vivo gene transfer of mST2 can be applicable to use in a novel immunotherapy for allergic diseases. [source] Airway eosinophilia is not a requirement for allergen-induced airway hyperresponsivenessCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2000Tournoy Background House dust mites (HDMs) are the major source of perennial allergens causing human allergic asthma. Animal models mimicking as closely as possible the allergic features observed in human asthma are therefore interesting tools for studying the immunological and pathophysiological mechanisms involved. Especially the role of eosinophils and allergen-specific immunoglobulin (Ig) E in the pathophysiology of airway hyperresponsiveness (AHR) remains a subject of intense debate. Objective To develop a mouse model of allergic airway inflammation and hyperresponsiveness based on the use of purified house dust mite allergen (Der p 1) as clinical relevant allergen. Furthermore, we studied the effects of low dose allergen exposure on the airway eosinophilia and AHR. Methods On day 0, C57Bl/6 mice were immunized with purified Der p 1 intraperitoneally. From day 14,20, the mice were exposed daily to a 30-min aerosol of different concentrations of house dust mite extract. Results Mice, actively immunized with Der p 1 and subsequently exposed to HDM aerosols, developed AHR, eosinophil infiltration of the airways and allergen-specific IgE. Moreover, lowering the concentration of the HDM aerosol also induced AHR and IgE without apparent eosinophil influx into the airways. Der p 1-sensitized mice exposed to PBS produced IgE, but did not show AHR or eosinophil influx. Conclusion This in vivo model of HDM-induced allergic airway changes suggests that AHR is not related to either eosinophil influx or allergen-specific serum IgE, thereby reducing the importance of these factors as essential elements for allergic AHR. [source] Glucocorticoid-induced TNFR family-related protein (GITR) activation exacerbates murine asthma and collagen-induced arthritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2005Manish Patel Abstract Glucocorticoid-induced TNFR family-related protein (GITR) is expressed at low levels on resting T cells, B cells and macrophages but at high levels on regulatory T cells (Treg). Although GITR expression is up-regulated on CD4+ effector cells upon activation, the role of GITR in Th1 and Th2 cell development is unclear. We report here that activation of GITR signalling by anti-GITR antibody markedly enhanced the induction of both Th1 and Th2 cytokine production by naive CD4+CD25, T cells. Consistent with this observation, anti-GITR antibody significantly enhanced the expression of the key Th1 (T-bet) and Th2 (GATA3) transcription factors in vitro. Administration of anti-GITR mAb in a murine model of arthritis significantly exacerbated the severity and onset of joint inflammation with elevated production of TNF-,, IFN-,, IL-5, and collagen-specific IgG1. Administration of anti-GITR mAb also significantly exacerbated murine allergic airways inflammation with elevated production of OVA-specific IFN-,, IL-2, IL-4, IL-5, and IgE. Finally, we demonstrated that adoptive transfer of CD4+GITR+ T cells effectively abolished airway inflammation induced in SCID mice reconstituted with CD4+GITR, T cells. Our results therefore provide direct evidence that GITR can modulate both Th1- and Th2-mediated inflammatory diseases, and may be a potential target for therapeutic intervention. [source] Allergic sensitization is enhanced in early life through toll-like receptor 7 activationCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2009S. Phipps Summary Background Prospective cohort studies suggest that children hospitalized in early life with severe infections are significantly more likely to develop recurrent wheezing and asthma. Objective Using an inhalational mouse model of allergic airways inflammation, we sought to determine the effect of viral and bacterial-associated molecular patterns on the magnitude of the allergic inflammatory response and whether this effect was age dependent. Methods BALB/c mice were sensitized by intranasal administration of endotoxinlow ovalbumin (OVA) in the absence or presence of viral single-stranded (ss)RNA, lipoteichoic acid or flagellin as neonates (within the first 24 h of life) or as weanlings (4 weeks of age). Mice were challenged four times with OVA at 6 weeks of age and end-points (bronchoalveolar lavage cytology, histology, antigen-specific T and B cell responses) determined at 7 weeks of age. Results Inhalational sensitization (<24 h or 4 weeks of age) and challenge with OVA induced a mild allergic inflammatory response in the airways as indicated by increased numbers of eosinophils and mucus cells, elevated serum OVA-specific IgG1, and production of T helper 2 (Th2) cytokines. Mice sensitized to endotoxinlow OVA at birth in the presence of ssRNA or lipoteichoic acid, but not flagellin, showed an increase in the numbers of airway and tissue eosinophils, mucus producing cells and antigen-specific production of IL-13 as compared with mice exposed only to endotoxinlow OVA. By contrast, all three TLR ligands failed to increase the magnitude of OVA-induced allergic inflammation in mice sensitized as weanlings. Conclusions Recognition of distinct microbial-associated patterns in early life may preferentially promote the de novo differentiation of bystander, antigen-specific CD4+ T cells toward a Th2 phenotype, and promote an asthma-like phenotype upon cognate antigen exposure in later life. [source] | ||||||||||||||||||||||