Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin

Julie B. Sedgwick, Rose F. Vrtis, Kristyn J. Jansen, Hirohito Kita, Kathleen Bartemes, William W. Busse

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background One mechanism of the eosinophil's contribution to airway inflammation in asthma is through release of cationic granule proteins to cause airway injury. Differences in either the intracellular concentration of granule proteins or the extent of activated degranulation between eosinophils from healthy patients and those with allergy and asthma could, therefore, relate to fundamental differences in this cell's function. Objective To identify phenotypic differences in eosinophil-derived neurotoxin (EDN) content and release in eosinophils from healthy patients, those with allergy, and those with allergy and asthma. Methods Peripheral blood eosinophils were isolated by negative anti-CD16 selection. Total intracellular and cytokine-activated release of EDN protein was measured by radioimmunoassay. EDN mRNA was assessed by real-time PCR. Results Eosinophils from patients with asthma contained significantly more EDN per cell than comparable cells from healthy patients, those with allergy but without asthma, or those with asthma treated with inhaled corticosteroids, but they had concentrations similar to airway eosinophils isolated from bronchoalveolar lavage fluid 48 hours after segmental bronchoprovocation with allergen. Furthermore, this increased granule protein was reflected in more EDN degranulation by IL-5- or GM-CSF-activated eosinophils when calculated as nanograms of protein secreted but not when calculated as a percentage of total EDN release. Levels of EDN mRNA were similar in all subject groups. Conclusions These data suggest that peripheral blood eosinophils from subjects with untreated asthma have increased inflammatory capacity, as reflected by greater intracellular concentrations of EDN.

Original languageEnglish (US)
Pages (from-to)568-574
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume114
Issue number3
DOIs
StatePublished - Sep 2004

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Eosinophil-Derived Neurotoxin
Eosinophils
Asthma
Hypersensitivity
Proteins
Messenger RNA
Interleukin-5
Bronchoalveolar Lavage Fluid
Granulocyte-Macrophage Colony-Stimulating Factor
Allergens
Radioimmunoassay
Real-Time Polymerase Chain Reaction
Adrenal Cortex Hormones
Cytokines
Inflammation

Keywords

  • AA
  • AA subjects treated with ICS
  • AA+ICS
  • allergic rhinitis
  • AR
  • asthma
  • BAL
  • corticosteroids
  • degranulation
  • Eosinophil
  • eosinophil-derived neurotoxin
  • hypereosinophilic syndrome
  • Patients with mild allergic asthma
  • Subjects with allergic rhinitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin. / Sedgwick, Julie B.; Vrtis, Rose F.; Jansen, Kristyn J.; Kita, Hirohito; Bartemes, Kathleen; Busse, William W.

In: Journal of Allergy and Clinical Immunology, Vol. 114, No. 3, 09.2004, p. 568-574.

Research output: Contribution to journalArticle

Sedgwick, Julie B. ; Vrtis, Rose F. ; Jansen, Kristyn J. ; Kita, Hirohito ; Bartemes, Kathleen ; Busse, William W. / Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin. In: Journal of Allergy and Clinical Immunology. 2004 ; Vol. 114, No. 3. pp. 568-574.
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AB - Background One mechanism of the eosinophil's contribution to airway inflammation in asthma is through release of cationic granule proteins to cause airway injury. Differences in either the intracellular concentration of granule proteins or the extent of activated degranulation between eosinophils from healthy patients and those with allergy and asthma could, therefore, relate to fundamental differences in this cell's function. Objective To identify phenotypic differences in eosinophil-derived neurotoxin (EDN) content and release in eosinophils from healthy patients, those with allergy, and those with allergy and asthma. Methods Peripheral blood eosinophils were isolated by negative anti-CD16 selection. Total intracellular and cytokine-activated release of EDN protein was measured by radioimmunoassay. EDN mRNA was assessed by real-time PCR. Results Eosinophils from patients with asthma contained significantly more EDN per cell than comparable cells from healthy patients, those with allergy but without asthma, or those with asthma treated with inhaled corticosteroids, but they had concentrations similar to airway eosinophils isolated from bronchoalveolar lavage fluid 48 hours after segmental bronchoprovocation with allergen. Furthermore, this increased granule protein was reflected in more EDN degranulation by IL-5- or GM-CSF-activated eosinophils when calculated as nanograms of protein secreted but not when calculated as a percentage of total EDN release. Levels of EDN mRNA were similar in all subject groups. Conclusions These data suggest that peripheral blood eosinophils from subjects with untreated asthma have increased inflammatory capacity, as reflected by greater intracellular concentrations of EDN.

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