CC chemokine ligand 1 promotes recruitment of eosinophils but not Th2 cells during the development of allergic airways disease.
One of the characteristic features of allergic asthma is recruitment of large numbers of inflammatory cells including eosinophils and Th2 lymphocytes to the lung. This influx of inflammatory cells is thought to be a controlled and coordinated process mediated by chemokines and their receptors. It is thought that distinct, differential expression of chemokine receptors allows selective migration of T cell subtypes in response to the chemokines that bind these receptors. Th2 cells preferentially express CCR8 and migrate selectively to its ligand, CC chemokine ligand (CCL)1. We studied the role of the CCR8 ligand, CCL1, in the specific recruitment of Th2 cells and eosinophils to the lung in a murine model of allergic airway disease. We have demonstrated for the first time that CCL1 is up-regulated in the lung following allergen challenge. Moreover, a neutralizing Ab to CCL1 reduced eosinophil migration to the lung, but had no effect on recruitment of Th2 cells following allergen challenge. In addition, there was no change in airway hyperresponsiveness or levels of Th2 cytokines. In a Th2 cell transfer system of pulmonary inflammation, anti-CCL1 also failed to affect recruitment of Th2 cells to the lung following allergen challenge. Significantly, intratracheal instillation of rCCL1 increased recruitment of eosinophils but not Th2 cells to the lung in allergen-sensitized and -challenged mice. In summary, our results indicate that CCL1 is important for the pulmonary recruitment of eosinophils, rather than allergen-specific Th2 cells, following allergen challenge.
Bishop
Benjamin
B
Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, London, United Kingdom.
Lloyd
Clare M
CM
D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology; D054402:Chemokine CCL1; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007275:Injections, Intravenous; D007442:Intubation, Intratracheal; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010993:Plethysmography, Whole Body; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000485:Allergens; C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D019742:Chemokines, CC; D016207:Cytokines; D007106:Immune Sera; D008024:Ligands; D010047:Ovalbumin