Expression of the C-C chemokine receptor CCR3 in human airway epithelial cells.
Chemokine-induced eosinophil chemotaxis is mediated primarily through the C-C chemokine receptor, CCR3. We have now detected CCR3 immunoreactivity on epithelial cells in biopsies of patients with asthma and other respiratory diseases. CCR3 mRNA was detected by Northern blot analysis after TNF-alpha stimulation of the human primary bronchial epithelial cells as well as the epithelial cell line, BEAS-2B; IFN-gamma potentiated the TNF-alpha-induced expression. Western blots and flow cytometry confirmed the expression of CCR3 protein. This receptor is functional based on studies demonstrating eotaxin-induced intracellular Ca(2+) flux and tyrosine phosphorylation of cellular proteins. The specificity of this functional response was confirmed by blocking these signaling events with anti-CCR3 mAb (7B11) or pertussis toxin. Furthermore, (125)I-eotaxin binding assay confirmed that CCR3 expressed on epithelial cells have the expected ligand specificity. These studies indicate that airway epithelial cells express CCR3 and suggest that CCR3 ligands may influence epithelial cell functions.
Stellato
C
C
Division of Clinical Immunology and Allergy, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
Brummet
M E
ME
Plitt
J R
JR
Shahabuddin
S
S
Baroody
F M
FM
Liu
M C
MC
Ponath
P D
PD
Beck
L A
LA
D001667:Binding, Competitive / Q000276:immunology; D001980:Bronchi / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D002460:Cell Line; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D002118:Calcium