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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2832-2839.
Prepublished online as a Blood First Edition Paper on July 8, 2004; DOI 10.1182/blood-2004-01-0268.


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Submitted January 23, 2004
Accepted June 21, 2004

Leukocyte Immunoglobulin-like Receptors: novel innate receptors for human basophil activation and inhibition

David E Sloane, Nicodemus Tedla, Muyiwa Awoniyi, Donald W MacGlashan, Luis Borges, K F Austen, and Jonathan P Arm*

Division of Rheumatology Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Partners Asthma Center, Brigham and Women's Hospital, Boston, MA, USA
Division of Rheumatology Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
Division of Rheumatology Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA
Asthma and Allergy Center, Johns Hopkins Hospital, Baltimore, MD, USA
Amgen Inc., Seattle, WA, USA
Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Rheumatology Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA; Partners Asthma Center, Brigham and Women's Hospital, Boston, MA, USA

* Corresponding author; email: jarm{at}rics.bwh.harvard.edu.

Basophils, recruited from the blood to tissues, have been implicated by their presence in diverse allergic disorders including bronchial asthma, allergic rhinitis, and cutaneous contact hypersensitivity. We hypothesized that like other leukocytes involved in inflammatory responses, basophils would express members of the Leukocyte Immunogloblin-like Receptor (LIR) family of immunoregulatory molecules on their cell surface. We identified LIR7, an activating member coupled to the common Fc receptor gamma chain, and LIR3, an inhibitory member containing cytoplasmic immunoreceptor tyrosine-based inhibitory motifs on these cells from human peripheral blood. Cross-linking of LIR7 resulted in the concentration-dependent net release of histamine (29.8±10.8%) and cysteinyl leukotrienes (cysLT) (31.4±8.7 ng/106 basophils) that were maximal at 30 minutes, and of Interleukin (IL) 4 (410.2±61.6 pg/106 basophils) that was maximal at 4 hours and comparable to the response initiated by cross-linking of the high affinity receptor for IgE (Fc{epsilon}RI). Co-ligation of LIR3 to LIR7 or to Fc{epsilon}RI by means of a second monoclonal antibody significantly inhibited net histamine release, cysLT production, and IL-4 generation. That LIR3 is profoundly counter-regulatory for both adaptive and innate receptors suggests a broad role in containment of the inflammatory response.


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