Eosinophil production of prostaglandin D2 in patients with aspirin-exacerbated respiratory disease

Xin Feng, Madison K. Ramsden, Julie Negri, Mary Grace Baker, Spencer C. Payne, Larry Borish, John W. Steinke

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Background Aspirin-exacerbated respiratory disease (AERD) differs from aspirin-tolerant disease in part because of eosinophilic tissue infiltration and overexpression of arachidonic acid metabolic pathway components that lead to enhanced secretion of cysteinyl leukotrienes and prostaglandin (PG) D2 observed constitutively and paradoxically in response to aspirin and other COX inhibitors. We have previously demonstrated the capacity of IFN-γ to drive cysteinyl leukotriene expression and response. Objective We investigated eosinophils as a source of PGD2 production in patients with AERD. Methods Eosinophils were enriched from tissue and peripheral blood obtained from control subjects, patients with aspirin-tolerant disease, and patients with AERD. mRNA was extracted and evaluated for expression of hematopoietic prostaglandin D synthase (hPGDS). Expression of hPGDS protein was confirmed with Western hybridization and immunofluorescence staining. Cells were stimulated with aspirin, and secretion of PGD2 was quantified. CD34+ progenitor cells were isolated and matured into eosinophils in the presence or absence of IFN-γ and hPGDS mRNA, and PGD2 release was measured. Results Gene expression analysis revealed that eosinophils from tissue and blood of patients with AERD display increased levels of hPGDS compared with asthmatic and control samples. Western hybridization confirmed the increase in hPGDS mRNA translated to increased protein expression. Immunofluorescence confirmed mast cells and eosinophils from tissue of patients with AERD and asthma demonstrated hPGDS expression, with higher levels in eosinophils from patients with AERD. Incubation of eosinophils from blood and tissue with aspirin stimulated PGD2 release. IFN-γ–matured eosinophil progenitors showed enhanced hPGDS expression and increased levels of PGD2 release at baseline and after aspirin stimulation. Conclusions In addition to mast cells, eosinophils represent an important source of PGD2 in patients with AERD and identify a new target for therapeutic intervention.

Original languageEnglish
Pages (from-to)1089-1097.e3
JournalJournal of Allergy and Clinical Immunology
Volume138
Issue number4
DOIs
StatePublished - 1 Oct 2016
Externally publishedYes

Keywords

  • Aspirin-exacerbated respiratory disease
  • aspirin-tolerant asthma
  • chronic sinusitis
  • cytokines
  • eosinophils
  • nasal polyps
  • prostaglandin D

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