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

Yokoi, Hidenori; Choi, Oksoon H; Hubbard, Walter; Lee, Hyun-Sil; Canning, Brendan J; Lee, Hyun H; Ryu, Seung-Duk; von Gunten, Stephan; Bickel, Carol A; Hudson, Sherry A; Macglashan, Donald W; Bochner, Bruce S (2008). Inhibition of FcepsilonRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement. Journal of allergy and clinical immunology, 121(2), 499-505.e1. St. Louis, Mo.: Mosby 10.1016/j.jaci.2007.10.004

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
UniBE Contributor:	von Gunten, Stephan
ISSN:	0091-6749
ISBN:	18036650
Publisher:	Mosby
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:04
Last Modified:	05 Dec 2022 14:19
Publisher DOI:	10.1016/j.jaci.2007.10.004
PubMed ID:	18036650
Web of Science ID:	000253337800033
URI:	https://boris.unibe.ch/id/eprint/27724 (FactScience: 110513)