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Siglec‐7 on peripheral blood eosinophils: Surface expression and function
Author(s) -
Legrand Fanny,
Landolidine,
Zaffran Ilan,
Emeh Robert O.,
Chen Elizabeth,
Klion Amy D.,
LeviSchaffer Francesca
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13730
Subject(s) - eosinophil , siglec , eosinophil cationic protein , eosinophil peroxidase , immunology , peripheral blood mononuclear cell , biology , microbiology and biotechnology , chemistry , in vitro , immune system , biochemistry , asthma
Abstract Background Siglec‐7 is an inhibitory receptor ( IR ) expressed on human blood eosinophils. Whereas activation of other IR s, including Siglec‐8 and CD 300a, has been shown to downregulate eosinophil function, little is known about the role of Siglec‐7 on human eosinophils. Objective To examine Siglec‐7 expression and function in eosinophils from normal ( ND ) and eosinophilic ( EO ) donors. Methods Eosinophil expression of Siglec‐7 was quantified by flow cytometry and quantitative PCR . Soluble Siglec‐7 (sSiglec‐7) levels were measured by ELISA in serum. The effect of Siglec‐7 on eosinophil viability and degranulation was assessed in vitro by AnnexinV‐ FITC /7‐ AAD staining and by measuring GM ‐ CSF ‐induced mediator release in culture supernatants. Signal transduction was studied by Western blot. Results Siglec‐7 was expressed ex vivo on blood eosinophils from all eosinophilic and normal individuals studied. Siglec‐7 surface, but not SIGLEC ‐7 mRNA expression, was correlated with absolute eosinophil count ( AEC ). Siglec‐7 was upregulated on purified eosinophils after in vitro stimulation with GM ‐ CSF or IL ‐5. Serum sSiglec‐7 was detectable in 133/144 subjects tested and correlated with AEC . Siglec‐7 cross‐linking inhibited GM ‐ CSF ‐induced release of eosinophil peroxidase, TNF ‐α, and IL ‐8 (n = 7–8) but did not promote eosinophil apoptosis (n = 5). Finally, Siglec‐7 cross‐linking on GM ‐ CSF ‐activated eosinophils induced phosphorylation of SHP ‐1 and de‐phosphorylation of ERK 1/2 and p38. Conclusions Siglec‐7 is constitutively expressed on human eosinophils and downmodulates eosinophil activation. Targeting of Siglec‐7 on eosinophils might enhance treatment efficacy in eosinophil‐driven disorders. Conversely, therapeutic interventions that inhibit Siglec‐7 could have unanticipated consequences and promote eosinophilic inflammation.