The role of eosinophils in the pathogenesis of asthma

Seminario, Maria Cristina; Gleich, Gerald J.

doi:10.1016/0952-7915(94)90005-1

Cited by 123 publications

(78 citation statements)

References 37 publications

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“…Southern Hybridization-Genomic DNA was isolated from venous blood of cynomolgus 2 and rhesus macaques (Macaca fascicularis and Macaca mulatta, respectively; Merck Research Laboratories, in-house colony) using the QIAamp DNA blood kit (Qiagen, Valencia, CA). Also, cynomolgus macaque DNA was purchased from Therion (Troy, NY), and rhesus macaque DNA was purchased from CLONTECH (Palo Alto, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Hybridoma supernatant (50 l), purified anti-macaque CCR3 mAbs, mouse IgG (ICN) (negative control), or mouse anti-human CD11b (BD Biosciences; clone ICRF44), all at 3 g/ml, was then added to the cells incubated at room temperature for 30 min. Cells were washed, and then fluorescein isothiocyanate-labeled goat F(abЈ) 2 anti-mouse IgG (5 g/ml; ICN) was added to the cells and incubated at room temperature for 30 min. For the rhesus macaque PBMCs, R-phycoerythrin-conjugated mouse anti-human CD3 mAb (clone SP34; BD Biosciences) was incubated as above.…”

Section: Rhesus Macaque Whole Blood Gated Autofluorescence Forward Scmentioning

confidence: 99%

“…In the pathophysiology of the disease, a chronic inflammatory condition persists in the airways of most patients, which involves a complex interplay between blood leukocytes, airway epithelial cells, and bronchial smooth muscle cells. One of the most striking aspects of asthma is the selective accumulation and activation of distinct subtypes of leukocytes into the airways, particularly eosinophils, and it is these cells that are postulated to play a key role in the pathophysiology of the disease (1,2).…”

mentioning

confidence: 99%

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Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

Zhang

Soares

Guan

et al. 2002

Journal of Biological Chemistry

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Eosinophils are major effector cells implicated in a number of chronic inflammatory diseases in humans, particularly bronchial asthma and allergic rhinitis. The ␤-chemokine receptor C-C chemokine receptor 3 (CCR3) provides a mechanism for the selective recruitment of eosinophils into tissue and thus has recently become an attractive biological target for therapeutic intervention. In order to develop in vivo models of inflammatory diseases, it is essential to identify and characterize the homologues of human eotaxin (C-C chemokine ligand 11) and CCR3 from other species, such as non-human primates. Accordingly, we cloned the macaque eotaxin and CCR3 genes and revealed that they were 91 and 92% identical at the amino acid level to their human homologues, respectively. Macaque CCR3 expressed in the murine pre-B L1-2 cell line bound macaque eotaxin with high affinity (K d ‫؍‬ 0.1 nM) and exhibited a robust eotaxin-induced Ca 2؉ flux and chemotaxis. Characterization of ␤-chemokines on native macaque CCR3 on eosinophils was performed by means of eotaxin-induced shape change in whole blood using a novel signaling assay known as gated autofluorescence forward scatter. Additionally, mAbs were raised against macaque CCR3 using two different immunogens: a 30-amino acid synthetic peptide derived from the predicted NH 2 terminus of macaque CCR3 and intact macaque CCR3-transfected cells. These anti-macaque CCR3 monoclonal antibodies exhibited potent antagonist activity in receptor binding and functional assays. The characterization of the macaque eotaxin/CCR3 axis and development of antagonistic anti-macaque CCR3 monoclonal antibodies will facilitate the development of CCR3 small molecule antagonists with the hope of ameliorating chronic inflammatory diseases in humans.

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Section: Methodsmentioning

confidence: 99%

Section: Rhesus Macaque Whole Blood Gated Autofluorescence Forward Scmentioning

confidence: 99%

mentioning

confidence: 99%

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Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

Zhang

Soares

Guan

et al. 2002

Journal of Biological Chemistry

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“…There is now substantial evidence that eosinophils are major effector cells in asthma (2)(3)(4), and an understanding of the mechanisms by which eosinophils accumulate and are activated in airway tissue is fundamental to our understanding of the pathogenesis of this disease. Adhesion molecules play an essential role in eosinophil recruitment (5,6) and are also considered to play a critical part in eosinophil activation (7)(8)(9).…”

mentioning

confidence: 99%

TNF-α Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for α5β1 Integrin

Burke‐Gaffney

Blease²,

Hartnell³

et al. 2002

The Journal of Immunology

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Cooperative action of inflammatory mediators and adhesion molecules orchestrates eosinophil recruitment during allergic inflammation in the airways. This study investigated the mechanisms involved in increasing eosinophil adhesion to human bronchial epithelial cells (HBEC) following priming and activation of eosinophils with TNF-α and complement protein C5a, respectively. Under primed conditions, eosinophil adhesion increased 3-fold from basal (16%), and the effect was significantly greater (p < 0.05) than the increase following stimulation with C5a alone (2-fold). Eosinophil contact with HBEC was essential for priming. In contrast to C5a, adhesion of eotaxin-stimulated eosinophils to HBEC was not primed with TNF-α nor IL-5, a known eosinophil-priming agent. Priming caused activation of αMβ2 integrin; mAb against either the common β2 integrin subunit or its ICAM-1 ligand reduced the primed component of adhesion. Using mAbs against β1 or α5, but not α4 integrin subunit, together with anti-β2 integrin mAb, reduced stimulated adhesion to basal levels. Cross-linking α5β1 integrin increased αMβ2 integrin-dependent adhesion of eosinophils. There are no known adhesion molecule ligands of α5β1 integrin expressed on HBEC; however, fibronectin, the major matrix protein ligand for α5β1 integrin, was detected in association with HBEC monolayers. A mAb against fibronectin, in combination with anti-β2 integrin mAb, reduced adhesion to basal levels. In conclusion, α5β1 integrin may provide a contact-dependent costimulus for eosinophil priming that, together with TNF-α, potentiated C5a activation of αMβ2 integrin and increased eosinophil adhesion to ICAM-1. Fibronectin, associated with HBEC, may act as a ligand for α5β1 integrin. Dual regulation of eosinophil priming may prevent inappropriate activation of eosinophils in the circulation.

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“…Much is known regarding how eosinophils markedly and widely infiltrated in the lower airway play a crucial role in sophisticated pathogenesis of allergic asthma [24,25]. In experimentally-induced asthma models using standard inbred strains of rodents, the eosinophil response and airway hyperresponsiveness to acetylcholine or methacholine are induced, but the grade of the phenomena is generally limited.…”

Section: Discussionmentioning

confidence: 99%

Atopic NC/Nga Mice as a Model for Allergic Asthma: Severe Allergic Responses by Single Intranasal Challenge with Protein Antigen.

Iwasaki

Tanaka

Itakura

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. Since certain characters of allergic asthma are common with other allergic disorders like atopic dermatitis, the possible relationship in etiology is expected. Herein, we investigated whether NC/Nga mice, an inherent animal model for human atopic dermatitis, are inclined to allergic asthma. A single intranasal challenge of NC/Nga mice immunized with ovalbumin (OVA) resulted in an increase in plasma levels of OVA-specific IgE, and typical pathological aspects of allergic asthma characterized by infiltration of numerous eosinophils, mucus hyper production of bronchial epithelial cells. Moreover, airway hyperresponsiveness to inhaled acetylcholine and marked enhancement of airway resistance after the challenge were observed as compared to control BALB/c mice. Delayed expression of mRNA of eosinophil active chemokines, interleukin-5, eotaxin, macrophage inflammatory protein-1α in concert with eosinophilia was determined in the lung of NC/Nga mice. These results suggest that asthmatic responses developed in NC/Nga mice challenged with OVA are very similar to human allergic asthma, and that NC/Nga mice are a useful model to elucidate various aspects of allergic asthma. KEY WORDS: allergy, cytokine, eosinophil, in vivo animal model, lung.

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The role of eosinophils in the pathogenesis of asthma

Cited by 123 publications

References 37 publications

Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies

TNF-α Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for α5β1 Integrin

Atopic NC/Nga Mice as a Model for Allergic Asthma: Severe Allergic Responses by Single Intranasal Challenge with Protein Antigen.

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