Inhibition of FcϵRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement

Hidenori Yokoi, Oksoon H. Choi, Walter Hubbard, Hyun Sil Lee, Brendan J. Canning, Hyun H. Lee, Seung Duk Ryu, Stephan von Gunten, Carol A. Bickel, Sherry A. Hudson, Donald W. MacGlashan, Bruce S. Bochner

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of glycan-binding inhibitory receptors, and among them, Siglec-8 is selectively expressed on human eosinophils, basophils, and mast cells. On eosinophils, Siglec-8 engagement induces apoptosis, but its function on mast cells is unknown. Objective: We sought to study the effect of Siglec-8 engagement on human mast cell survival and mediator release responses. Methods: Human mast cells were generated from CD34+ precursors. Apoptosis was studied by using flow cytometry. Mast cell mediator release or human lung airway smooth muscle contraction was initiated by Fcε{lunate}RI cross-linking with or without preincubation with Siglec-8 or control antibodies, and release of mediators was analyzed along with Ca++ flux. RBL-2H3 cells transfected with normal and mutated forms of Siglec-8 were used to study how Siglec-8 engagement alters mediator release. Results: Siglec-8 engagement failed to induce human mast cell apoptosis. However, preincubation with Siglec-8 mAbs significantly (P < .05) inhibited Fcε{lunate}RI-dependent histamine and prostaglandin D2 release, Ca++ flux, and anti-IgE-evoked contractions of human bronchial rings. In contrast, release of IL-8 was not inhibited. Siglec-8 ligation was also shown to inhibit β-hexosaminidase release and Ca++ flux triggered through Fcε{lunate}RI in RBL-2H3 cells transfected with full-length human Siglec-8 but not in cells transfected with Siglec-8 containing a tyrosine to phenylalanine point mutation in the membrane-proximal immunoreceptor tyrosine-based inhibitory motif domain. Conclusion: These data represent the first reported inhibitory effects of Siglec engagement on human mast cells.

Original languageEnglish (US)
Pages (from-to)499-505.e1
JournalJournal of Allergy and Clinical Immunology
Volume121
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • IgE receptor
  • Siglec
  • histamine
  • immunoreceptor tyrosine-based inhibitory motif
  • mast cell
  • prostaglandin D

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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