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J Allergy Clin Immunol. 2008 Feb;121(2):499-505.e1. Epub 2007 Nov 26.

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

Author information

1
Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, and the Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.

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 FcepsilonRI 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 FcepsilonRI-dependent histamine and prostaglandin D(2) 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 beta-hexosaminidase release and Ca++ flux triggered through FcepsilonRI 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.

PMID:
18036650
DOI:
10.1016/j.jaci.2007.10.004
[Indexed for MEDLINE]

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