| Human airway eosinophils respond to chemoattractants with greater eosinophil-derived neurotoxin release, adherence to fibronectin, and activation of the Ras-ERK pathway when compared with blood eosinophils. | |
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MedLine Citation:
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PMID: 20495064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human blood eosinophils exposed ex vivo to hematopoietic cytokines (e.g., IL-5 or GM-CSF) subsequently display enhanced responsiveness to numerous chemoattractants, such as chemokines, platelet-activating factor, or FMLP, through a process known as priming. Airway eosinophils, obtained by bronchoalveolar lavage after segmental Ag challenge, also exhibit enhanced responsiveness to selected chemoattractants, suggesting that they are primed during cell trafficking from the blood to the airway. Earlier work has shown that chemoattractants stimulate greater activation of ERK1 and ERK2 following IL-5 priming in vitro, thus revealing that ERK1/ERK2 activity can be a molecular readout of priming under these circumstances. Because few studies have examined the intracellular mechanisms regulating priming as it relates to human airway eosinophils, we evaluated the responsiveness of blood and airway eosinophils to chemoattractants (FMLP, platelet-activating factor, CCL11, CCL5, CXCL8) with respect to degranulation, adherence to fibronectin, or Ras-ERK signaling cascade activation. When compared with blood eosinophils, airway eosinophils exhibited greater FMLP-stimulated eosinophil-derived neurotoxin release as well as augmented FMLP- and CCL11-stimulated adherence to fibronectin. In airway eosinophils, FMLP, CCL11, and CCL5 stimulated greater activation of Ras or ERK1/ERK2 when compared with baseline. Ras activation by FMLP in blood eosinophils was also enhanced following IL-5 priming. These studies are consistent with a model of in vivo priming of eosinophils by IL-5 or related cytokines following allergen challenge, and further demonstrate the key role of priming in the chemoattractant-stimulated responses of eosinophils. These data also demonstrate the importance of the Ras-ERK signaling pathway in the regulation of eosinophil responses to chemoattractants in the airway. Human airway eosinophils respond to several chemoattractants with increased activation of the Ras-ERK cascade, eosinophil-derived neurotoxin release, and adherence to fibronectin relative to blood eosinophils. |
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Authors:
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Mary Ellen Bates; Julie B Sedgwick; Yiming Zhu; Lin Ying Liu; Rose G Heuser; Nizar N Jarjour; Hirohito Kita; Paul J Bertics |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2010-05-21 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 184 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-07 Completed Date: 2010-06-18 Revised Date: 2011-09-28 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 7125-33 Citation Subset: AIM; IM |
Affiliation:
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Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Cell Adhesion / immunology Cell Degranulation / immunology Chemotactic Factors / immunology, metabolism Chemotaxis, Leukocyte / immunology* Enzyme Activation / immunology* Eosinophil-Derived Neurotoxin / biosynthesis*, immunology Eosinophils / immunology, metabolism* Extracellular Signal-Regulated MAP Kinases / immunology, metabolism Fibronectins / immunology, metabolism Humans Immunoblotting Lung / cytology, immunology* Middle Aged Signal Transduction / immunology* Young Adult ras Proteins / immunology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1UL1RR025011/RR/NCRR NIH HHS; AI070503/AI/NIAID NIH HHS; AI34486/AI/NIAID NIH HHS; HL069116/HL/NHLBI NIH HHS; HL088594/HL/NHLBI NIH HHS; HL56396/HL/NHLBI NIH HHS; P01 HL088594-01A10003/HL/NHLBI NIH HHS; P01 HL088594-02/HL/NHLBI NIH HHS; P50 HL056396-010004/HL/NHLBI NIH HHS; R01 AI034486-06/AI/NIAID NIH HHS; R01 HL069116-01/HL/NHLBI NIH HHS; U19 AI070503-010002/AI/NIAID NIH HHS; UL1 RR025011-01/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemotactic Factors; 0/Fibronectins; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.1.-/Eosinophil-Derived Neurotoxin; EC 3.6.5.2/ras Proteins |
| Comments/Corrections | |
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