CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13.
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 (Fc epsilon RI) 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 Fc epsilon RI cross-linkage (concomitantly with maximal surface CCR3 expression) increased Fc epsilon RI-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.
Price
Kursteen S
KS
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Friend
Daniel S
DS
Mellor
Elizabeth A
EA
De Jesus
Nidia
N
Watts
Gerald F M
GF
Boyce
Joshua A
JA
D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000096:biosynthesis*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism / Q000502:physiology*
C515350:CCR3 protein, human; D018793:Interleukin-13; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D007073:Immunoglobulin E