Enhanced airway Th2 response after allergen challenge in mice deficient in CC chemokine receptor-2 (CCR2). 2001

Y Kim, and Sung Ss, and W A Kuziel, and S Feldman, and S M Fu, and C E Rose
Division of Pulmonary and Critical Care Medicine, and Division of Rheumatology and Immunology, University of Virginia Health System, Charlottesville, VA 22908, USA.

To evaluate the role of CCR2 in allergic asthma, mutant mice deficient in CCR2 (CCR2(-/-)) and intact mice were sensitized with i.p. OVA with alum on days 0 and 7, and challenged by inhalation with nebulization of either OVA or saline. Airway hyperreactivity, measured by the methacholine-provoked increase in enhanced pause, was significantly increased (p < 0.05) in OVA-challenged CCR2(-/-) mutant mice, compared with comparably challenged CCR2(+/+) mice. OVA-challenged CCR2(-/-) mutants also were also found to have enhanced bronchoalveolar lavage fluid eosinophilia, peribronchiolar cellular cuffing, and Ig subclass switching, with increase in OVA-specific IgG(1) and IgE. In addition, RNase protection assay revealed increased whole lung expression of IL-13 in OVA-challenged CCR2(-/-) mutants. Unexpectedly, serum monocyte chemotactic protein-1 levels were 8-fold higher in CCR2(-/-) mutants than in CCR2(+/+) mice sensitized to OVA, but OVA challenge had no additional effect on circulating monocyte chemotactic protein-1 in either genotype. Ag stimulation of lymphocytes isolated from OVA-sensitized CCR2 mutants revealed a significant increase (p < 0.05) in IL-5 production, which differed from OVA-stimulated lymphocytes from sensitized CCR2(+/+) mice. These experiments demonstrate an enhanced response in airway reactivity and in lung inflammation in CCR2(-/-) mutant mice compared with comparably sensitized and challenged CCR2(+/+) mice. These observations suggest that CC chemokines and their receptors are involved in immunomodulation of atopic asthma.

UI MeSH Term Description Entries
D007073 Immunoglobulin E An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). IgE
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D010047 Ovalbumin An albumin obtained from the white of eggs. It is a member of the serpin superfamily. Serpin B14
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal

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