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CC Chemokine Receptor 3 Mobilizes to the Surface of Human Mast Cells and Potentiates Immunoglobulin E–Dependent Generation of Interleukin 13

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital; and Departments of Medicine, Pediatrics, and Pathology, Harvard Medical School, Boston, Massachusetts

Address correspondence to: Joshua A. Boyce, M.D., Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Research Building, 1 Jimmy Fund Way, Boston, MA 02115. E-mail: Jboyce{at}RICS.bwh.harvard.edu

Eotaxins-1, -2, and -3 mediate the recruitment of blood-borne eosinophils to allergically inflamed tissues by binding CC chemokine receptor (CCR) 3. Mast cells (MCs) are resident tissue cells that also express CCR3. In the present study, we demonstrate that human (h) MCs in nasal polyps and cultured cord blood–derived hMCs express CCR3 not only on their surfaces but also in their secretory granules. Activation of hMCs mediated by the high-affinity Fc receptor for immunoglobulin (Ig)E (FcRI) increased the surface presentation of CCR3 within 1 h, with a parallel decrease in intracellular CCR3 as determined by flow cytometry on saponin-permeabilized hMCs. Recombinant eotaxin-1 alone did not induce histamine release or cytokine generation, and did not significantly augment IgE-dependent histamine release by interleukin (IL)-4–primed hMCs. Nevertheless, stimulation of hMCs with eotaxin-1 2 h after FcRI cross-linkage (concomitantly with maximal surface CCR3 expression) increased FcRI-dependent IL-13 generation by hMCs, compared with their replicates stimulated simultaneously with both agonists. Thus, hMCs may store CCR3 and rapidly mobilize it to their surface with IgE-dependent activation, providing a novel potential mechanism for enhanced hMC effector function, including IL-13 production.

Abbreviations: CC chemokine receptor 3, CCR3 • CXC chemokine receptor 4, CXCR4 • enzyme-linked immunosorbent assay, ELISA • high-affinity Fc receptors for IgE, FcRI • G-protein–coupled receptor, GPCR • Hanks' balanced salt solution containing 2% bovine serum albumin, HBA • human mast cell, hMC • human progenitor mast cell, hPrMC • immunoglobulin, Ig • interleukin, IL • mast cell, MC • median fluorescence intensity, MFI • phosphate-buffered saline, PBS • reverse transcriptase–polymerase chain reaction, RT-PCR • stem cell factor, SCF • stromal cell-derived factor, SDF

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