Airway eosinophilia is not a requirement for allergen‐induced airway hyperresponsiveness

Tournoy, Kurt G.; Kips, Johan; Schou, C.; Pauwels, Romain

doi:10.1046/j.1365-2222.2000.00772.x

Cited by 167 publications

(119 citation statements)

References 36 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…This may be due to the use of OVA peptide, which is a weaker immunogen with a single T epitope and without dominant B cell epitopes, thus limiting the participation of both T and B cells and the formation of immune complexes. Wilder et al (31) and more recently Tournoy et al (32) reported similar findings in mice immunized with limited frequency or Ag dose. In all cases relatively weak immune responses have been elicited.…”

Section: Discussionmentioning

confidence: 62%

See 1 more Smart Citation

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

Sung

Rose

2001

The Journal of Immunology

View full text Add to dashboard Cite

Dendritic cells (DC) are the primary APC responsible for the capture of allergens in the airways and the shuttling of processed allergens to the draining lymph nodes where Ag presentation and T cell activation take place. The mechanism of this Ag handling and presentation in asthma is poorly understood. In addition, the feasibility of asthma induction by DC priming has not been directly tested. In this report an asthma model using intratracheally (i.t.) injected splenic DC was used to address these issues. DC pulsed with a model Ag OVA or the major MHC class II-restricted OVA T epitope peptide OVA323–339 and instilled i.t. primed mice to exhibit asthma-like diseases. With OVA as the Ag, mice exhibit airway hyperresponsiveness (AHR), lung eosinophilia and inflammation, and pulmonary goblet cell hyperplasia. In OVA323–339-immunized mice, AHR and goblet cell hyperplasia were noted, with little eosinophilia and parenchymal inflammation. The latter finding provides evidence for dissociating AHR from eosinophilia. In both cases mediastinal node hypertrophy occurred, and high levels of Th2 cytokines were produced by the lung and mediastinal lymph node cells (LNC). Interestingly, mediastinal LNC also produced high levels of Th1 cytokines. Lung cells produced much less Th1 cytokines than these LNC. These results demonstrate that DC when introduced i.t. are potent in inducing asthma-like diseases by recruiting lymphocytes to the lung-draining lymph nodes and by stimulating Th2 responses and also suggest that the lung environment strongly biases T cell responses to Th2.

show abstract

Section: Discussionmentioning

confidence: 62%

“…In contrast to human asthma, asthma-like diseases in the mouse do not require the participation of IgE (2,3,(31)(32)(33). The presence of B cells is also not a prerequisite for the induction of asthmarelated symptoms (34).…”

Section: Discussionmentioning

confidence: 99%

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

Sung

Rose

2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The role of eosinophils in causing AHR has been controversial but has been assumed to be a critical determinant of AHR (6, 38 -40). However, several studies have shown that AHR can develop independently from the recruitment of eosinophils (4,(41)(42)(43)(44)(45)(46). In addition, it has been demonstrated that airway eosinophilia can occur without the development of AHR (7,47).…”

Section: Discussionmentioning

confidence: 99%

Critical Role for IL-13 in the Development of Allergen-Induced Airway Hyperreactivity

Walter¹,

McIntire²,

Berry

et al. 2001

The Journal of Immunology

378

257

View full text Add to dashboard Cite

Airway hyperresponsiveness to a variety of specific and nonspecific stimuli is a cardinal feature of asthma, which affects nearly 10% of the population in industrialized countries. Eosinophilic pulmonary inflammation, eosinophil-derived products, as well as Th2 cytokines IL-13, IL-4, and IL-5, have been associated with the development of airway hyperreactivity (AHR), but the specific immunological basis underlying the development of AHR remains controversial. Herein we show that mice with targeted deletion of IL-13 failed to develop allergen-induced AHR, despite the presence of vigorous Th2-biased, eosinophilic pulmonary inflammation. However, AHR was restored in IL-13−/− mice by the administration of recombinant IL-13. Moreover, adoptive transfer of OVA-specific Th2 cells generated from TCR-transgenic IL-13−/− mice failed to induce AHR in recipient SCID mice, although such IL-13−/− Th2 cells produced high levels of IL-4 and IL-5 and induced significant airway inflammation. These studies definitively demonstrate that IL-13 is necessary and sufficient for the induction of AHR and that eosinophilic airway inflammation in the absence of IL-13 is inadequate for the induction of AHR. Therefore, treatment of human asthma with antagonists of IL-13 may be very effective.

show abstract

“…Inflammation score was graded by three independent blinded investigators. The degree of peribronchial and perivascular inflammation was evaluated on a subjective scale of 0 to 3, as described elsewhere (Tournoy et al, 2000). A value of 0 was adjudged when no inflammation was detectable, a value of 1 for occasional cuffing with inflammatory cells, a value of 2 for most bronchi or vessels surrounded by thin layer (one to five cells) of inflammatory cells, and a value of 3 when most bronchi or vessels were surrounded by a thick layer (more than five cells) of inflammatory cells.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1

Lee

Lee²,

Kim³

et al. 2007

Exp Mol Med

View full text Add to dashboard Cite

Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage. Recently, we developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. COMP-Ang1 is more potent than native Ang1 in phosphorylating the tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 receptor in lung endothelial cells. We have used a mouse model for allergic airway disease to determine effects of COMP-Ang1 on allergen-induced bronchial inflammation and airway hyper-responsiveness. These mice develop the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, increased levels of Th2 cell cytokines (IL-4, IL-5, and IL-13), adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), and chemokines (eotaxin and RANTES), and increased vascular permeability. Intravenous administration of COMP-Ang1 reduced bronchial inflammation and airway hyper-responsiveness. In addition, the increased plasma extravasation in allergic airway disease was significantly reduced by the administration of COMP-Ang1. These results suggest that COMP-Ang1 attenuates airway inflammation and hyper-responsiveness, prevents vascular leakage, and may be used as a therapeutic agent in allergic airway disease.

show abstract

Airway eosinophilia is not a requirement for allergen‐induced airway hyperresponsiveness

Abstract: 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.

Cited by 167 publications

References 36 publications

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

Critical Role for IL-13 in the Development of Allergen-Induced Airway Hyperreactivity

Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1

Contact Info

Product

Resources

About