Kinetics of the development and recovery of the lung from IgE-mediated inflammation: dissociation of pulmonary eosinophilia, lung injury, and eosinophil-active cytokines.

Shaver, Joseph R.; Zangrilli, James; Cho, S K; Cirelli, Rosemary; Pollice, Mary; Hastie, Annette T.; Fish, James E.; Peters, Stephen P.

doi:10.1164/ajrccm.155.2.9032176

Cited by 61 publications

(32 citation statements)

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“…We had hypothesized that, because of the high concentration of IL-5 and GM-CSF in the human airway following segmental bronchoprovocation with Ag (23,24), STAT3 and STAT5 would be constitutively phosphorylated in airway eosinophils obtained after segmental bronchoprovocation with Ag. However, freshly isolated airway eosinophils, procured via segmental bronchoprovocation with Ag and lavage, were not detectably phosphorylated on tyrosine 705 of STAT3 or tyrosine 694 of STAT5, suggesting that these STAT proteins are not constitutively activated within the limits of detection by immunoblotting.…”

Section: Discussionmentioning

confidence: 99%

IL-5 and Granulocyte-Macrophage Colony-Stimulating Factor Activate STAT3 and STAT5 and Promote Pim-1 and Cyclin D3 Protein Expression in Human Eosinophils

Stout

Bates

Liu

et al. 2004

The Journal of Immunology

109

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Allergic inflammation is characterized by elevated eosinophil numbers and by the increased production of the cytokines IL-5 and GM-CSF, which control several eosinophil functions, including the suppression of apoptosis. The JAK/STAT pathway is important for several functions in hemopoietic cells, including the suppression of apoptosis. We report in this study that STAT3, STAT5a, and STAT5b are expressed in human eosinophils and that their signaling pathways are active following IL-5 or GM-CSF treatment. However, in airway eosinophils, the phosphorylation of STAT5 by IL-5 is reduced, an event that may be related to the reduced expression of the IL-5Rα on airway eosinophils. Furthermore, IL-5 and GM-CSF induced the protein expression of cyclin D3 and the kinase Pim-1, both of which are regulated by STAT-dependent processes in some cell systems. Pim-1 is more abundantly expressed in airway eosinophils than in blood eosinophils. Because Pim-1 reportedly has a role in the modulation of apoptosis, these results suggest that Pim-1 action is linked to the suppression of eosinophil apoptosis by these cytokines. Although cyclin D3 is known to be critical for cell cycle progression, eosinophils are terminally differentiated cells that do not proceed through the cell cycle. Thus, this apparent cytokine regulation of cyclin D3 suggests that there is an alternative role(s) for cyclin D3 in eosinophil biology.

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Section: Discussionmentioning

confidence: 99%

IL-5 and Granulocyte-Macrophage Colony-Stimulating Factor Activate STAT3 and STAT5 and Promote Pim-1 and Cyclin D3 Protein Expression in Human Eosinophils

Stout

Bates

Liu

et al. 2004

The Journal of Immunology

109

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“…All subjects underwent bronchoscopic lavage, biopsy, and challenge with ragweed as described previously (37,38). All subjects were premedicated with albuterol (four puffs by metered-dose inhaler) and inhaled and received topically applied lidocaine in the airways.…”

Section: Bronchoscopy Bal and Segmental Ag Challenge (Sac)mentioning

confidence: 99%

Differential Expression of TRAIL and TRAIL Receptors in Allergic Asthmatics Following Segmental Antigen Challenge: Evidence for a Role of TRAIL in Eosinophil Survival

Robertson¹,

Zangrilli

Steplewski³

et al. 2002

The Journal of Immunology

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Asthma is a chronic lung disease exhibiting airway obstruction, hyperresponsiveness, and inflammation, characterized by the infiltration of eosinophils into the airways and the underlying tissue. Prolonged eosinophilic inflammation depends on the balance between the cell’s inherent tendency to undergo apoptosis and the local eosinophil-viability enhancing activity. TRAIL, a member of the TNF family, induces apoptosis in most transformed cells; however, its role in health and disease remains unknown. To test the hypothesis that Ag-induced inflammation is associated with TRAIL/TRAIL-R interactions, we used a segmental Ag challenge (SAC) model in ragweed-allergic asthmatics and nonasthmatic patients and analyzed bronchoalveolar lavage (BAL) material for 2 wk. In asthmatic patients, the level of TRAIL in BAL fluid dramatically increased 24 h after SAC, which significantly correlated with BAL eosinophil counts. Immunohistochemical analysis of bronchial biopsies from asthmatic patients demonstrated that TRAIL staining was increased in epithelial, airway smooth muscle, and vascular smooth muscle cells and throughout the interstitial tissue after SAC. This was confirmed by quantitative immunocytochemical image analysis of BAL eosinophils and alveolar macrophages, which demonstrated that expression levels of TRAIL and DcR2 increased, whereas expression levels of the TRAIL-Rs DR4 and DR5 decreased in asthmatic subjects after SAC. We also determined that TRAIL prolongs eosinophil survival ex vivo. These data provide the first in vivo evidence that TRAIL expression is increased in asthmatics following Ag provocation and suggest that modulation of TRAIL and TRAIL-R interactions may play a crucial role in promoting eosinophil survival in asthma.

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“…9,10 This dual action of GM-CSF has encouraged its utilization in different vaccination strategies. 11 On the other hand, these same properties have implicated GM-CSF in myeloid leukemia and several inflammatory conditions such as asthma 12 and rheumatoid arthritis. 13 The actions of GM-CSF are mediated by specific receptors composed of 2 different subunits, a receptor ␣ chain (GMR␣), 14 which provides specificity and the major binding contact, and a ␤ chain (␤c), 15 which is common with the interleukin-3 (IL-3) and IL-5 receptors, promotes affinity conversion, and acts as the major signal transducer.…”

Section: Introductionmentioning

confidence: 98%

Molecular assembly of the ternary granulocyte-macrophage colony-stimulating factor receptor complex

McClure

Hercus

Cambareri

et al. 2003

Blood

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the production and functional activity of granulocytes and macrophages, properties that have encouraged its clinical use in bone marrow transplantation and in certain infectious diseases. Despite the importance of GM-CSF in regulating myeloid cell numbers and function, little is known about the exact composition and mechanism of assembly of the GM-CSF receptor complex. We have now produced soluble forms of the GM-CSF receptor ␣ chain (sGMR␣) and ␤ chain (s␤c) and utilized GM-CSF, the GM-CSF antagonist E21R (Glu21Arg), and the ␤c-blocking monoclonal antibody BION-1 to define the molecular assembly of the GM-CSF receptor complex. We found that GM-CSF and E21R were able to form low-affinity, binary complexes with sGMR␣, each having a stoichiometry of 1:1. Importantly, GM-CSF but not E21R formed a ternary complex with sGMR␣ and s␤c, and this complex could be disrupted by E21R. Significantly, sizeexclusion chromatography, analytical ultracentrifugation, and radioactive tracer experiments indicated that the ternary complex is composed of one s␤c dimer with a single molecule each of sGMR␣ and of GM-CSF. In addition, a hitherto unrecognized direct interaction between ␤c and GM-CSF was detected that was absent with E21R and was abolished by BION-1. These results demonstrate a novel mechanism of cytokine receptor assembly likely to apply also to interleukin-3 (IL-3) and IL-5 and have implications for our molecular understanding and potential manipulation of GM-CSF activation of its receptor. (Blood. 2003;101: 1308-1315)

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Kinetics of the development and recovery of the lung from IgE-mediated inflammation: dissociation of pulmonary eosinophilia, lung injury, and eosinophil-active cytokines.

Cited by 61 publications

References 0 publications

IL-5 and Granulocyte-Macrophage Colony-Stimulating Factor Activate STAT3 and STAT5 and Promote Pim-1 and Cyclin D3 Protein Expression in Human Eosinophils

IL-5 and Granulocyte-Macrophage Colony-Stimulating Factor Activate STAT3 and STAT5 and Promote Pim-1 and Cyclin D3 Protein Expression in Human Eosinophils

Differential Expression of TRAIL and TRAIL Receptors in Allergic Asthmatics Following Segmental Antigen Challenge: Evidence for a Role of TRAIL in Eosinophil Survival

Molecular assembly of the ternary granulocyte-macrophage colony-stimulating factor receptor complex

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