The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness.
CCR3 is a chemokine receptor initially thought specific to eosinophils but subsequently identified on TH2 cell subsets, basophils, mast cells, neural tissue, and some epithelia. Because of the prominent role of these cells in allergic disease, including asthma, we generated mice deficient in CCR3 to determine its contribution in a model of allergic airway disease. Here we show that CCR3 is important for the basal trafficking of eosinophils to the intestinal mucosa but not the lung. In contrast, CCR3 disruption significantly curtails eosinophil recruitment to the lung after allergen challenge, with the majority of the eosinophils being arrested in the subendothelial space. Further, a role for CCR3 in mast cell homing has been identified; after sensitization and allergen challenge, we find increased numbers of intraepithelial mast cells in the trachea of knockout mice. Physiologically, we find that the net result of these complex cell fates after sensitization and allergen challenge is a paradoxical increase in airway responsiveness to cholinergic stimulation. These data underscore a more complex role for CCR3 in allergic disease than was anticipated.
Humbles
Alison A
AA
Ina Sue Perlmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Lu
Bao
B
Friend
Daniel S
DS
Okinaga
Shoji
S
Lora
Jose
J
Al-Garawi
Amal
A
Martin
Thomas R
TR
Gerard
Norma P
NP
Gerard
Craig
C
D000485:Allergens / Q000276:immunology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D000485:Allergens; C515351:Ccr3 protein, mouse; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D010047:Ovalbumin