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Originally published online as doi:10.1189/jlb.0507314 on November 12, 2007

Published online before print November 12, 2007
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(Journal of Leukocyte Biology. 2008;83:334-343.)
© 2008 by Society for Leukocyte Biology

Differential expression of leukocyte immunoglobulin-like receptors on cord blood-derived human mast cell progenitors and mature mast cells

Nicodemus Tedla*,1, Chyh-Woei Lee{dagger}, Luis Borges{ddagger}, Carolyn L. Geczy* and Jonathan P. Arm{dagger}

* Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia;
{dagger} Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; and
{ddagger} Amgen Inc., Seattle, Washington, USA

1 Correspondence: Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052 Australia. E-mail: n.tedla{at}unsw.edu.au

The leukocyte Ig-like receptors (LILRs) comprise a family of cell-surface immunoregulatory receptors with activating and inhibitory members. The inhibitory LILRs possess cytoplasmic ITIMs that down-regulate signaling by nonreceptor tyrosine kinase cascades. The activating members have a truncated cytoplasmic domain and signal through the FcR{gamma} chain. We examined the expression of LILRs on human mast cells during their development in vitro. Progenitor mast cells expressed cell surface inhibitory LILRB1, -B2, -B3, and -B4 and activating LILRA1. However, although mature cord blood-derived mast cells (hMCs) had detectable mRNA encoding multiple LILRs, none were expressed on the cell surface. Culture of progenitor mast cells or hMCs with various cytokine combinations failed to retain or induce cell surface expression of the LILRs. It is interesting that hMCs expressed LILRB5 in cytoplasmic granules and upon cross-linking of the high-affinity IgE receptor, released LILRB5 into the culture medium. Our results demonstrate that LILRs are developmentally regulated in human mast cells and that LILRB5 is expressed in mast cell granules and the release of soluble LILRB5 following IgE FcR-dependent stimulation, which has potential for amplification of mast cell-dependent, inflammatory responses.

Key Words: immunoreceptor tyrosine-based inhibitory motifs • immunoreceptor tyrosine-based activating motifs • immune regulation • mast cell activation




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