Format

Send to

Choose Destination
Int Arch Allergy Immunol. 2018;177(1):16-28. doi: 10.1159/000488951. Epub 2018 Jun 7.

Characterization of Siglec-8 Expression on Lavage Cells after Segmental Lung Allergen Challenge.

Author information

1
Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
2
Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
3
Department of Medicine, Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Abstract

BACKGROUND:

Siglec-8 is present at a high level on human blood eosinophils and low level on blood basophils. Engagement of Siglec-8 on blood eosinophils causes its internalization and results in death. Siglec-8 is a potential therapeutic target in eosinophilic asthma.

OBJECTIVES:

The aim of this study was to determine Siglec-8 levels on eosinophils and basophils recruited during lung inflammation.

METHOD:

We analyzed surface Siglec-8 by flow cytometry on cells obtained by bronchoalveolar lavage (BAL) 48 h after segmental lung allergen challenge of human subjects with mild allergic asthma and used confocal microscopy to compare Siglec-8 distribution on BAL and blood eosinophils.

RESULTS:

Like their blood counterparts, BAL eosinophils had high unimodal surface Siglec-8, while BAL basophils had lower but detectable surface Siglec-8. BAL macrophages, monocytes, neutrophils, and plasmacytoid dendritic cells did not express surface Siglec-8. Microscopy of freshly isolated blood eosinophils demonstrated homogeneous Siglec-8 distribution over the cell surface. Upon incubation with IL-5, Siglec-8 on the surface of eosinophils became localized in patches both at the nucleopod tip and at the opposite cell pole. BAL eosinophils also had a patchy Siglec-8 distribution.

CONCLUSIONS:

We conclude that 48 h after segmental allergen challenge, overall levels of Siglec-8 expression on airway eosinophils resemble those on blood eosinophils, but with a patchier distribution, a pattern consistent with activation. Thus, therapeutic targeting of Siglec-8 has the potential to impact blood as well as lung eosinophils, which may be associated with an improved outcome in eosinophilic lung diseases.

KEYWORDS:

Airway; Basophil; Blood; Eosinophil; Flow cytometry

PMID:
29879704
PMCID:
PMC6105496
[Available on 2019-06-07]
DOI:
10.1159/000488951
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland
Loading ...
Support Center