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CC Chemokine Receptor-2 Is Not Essential for the Development of Antigen-Induced Pulmonary Eosinophilia and Airway Hyperresponsiveness¹

James A. MacLean^2,*, George T. De Sanctis, Kate G. Ackerman, Jeffrey M. Drazen, Alain Sauty^*, Elliot DeHaan^*, Francis H. Y. Green, Israel F. Charo^¶ and Andrew D. Luster^*

^* Center for Immunology and Inflammatory Disease, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Pulmonary and Critical Care Divisions, Brigham and Women’s Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02114; Department of Pathology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and ^¶ Gladstone Institute, University of California, San Francisco, CA 94141

Monocyte chemoattractant proteins-1 and -5 have been implicated as important mediators of allergic pulmonary inflammation in murine models of asthma. The only identified receptor for these two chemokines to date is the CCR2. To study the role of CCR2 in a murine model of Ag-induced asthma, we compared the pathologic and physiological responses of CCR2^-/- mice with those of wild-type (WT) littermates following immunization and challenge with OVA. OVA-immunized/OVA-challenged (OVA/OVA) WT and CCR2^-/- mice developed significant increases in total cells recovered by bronchoalveolar lavage (BAL) compared with their respective OVA-immunized/PBS-challenged (OVA/PBS) control groups. There were no significant differences in BAL cell counts and differentials (i.e., macrophages, PMNs, lymphocytes, and eosinophils) between OVA/OVA WT and CCR2^-/- mice. Serologic evaluation revealed no significant difference in total IgE and OVA-specific IgE between OVA/OVA WT mice and CCR2^-/- mice. Lung mRNA expression and BAL cytokine protein levels of IL-4, IL-5, and IFN- were also similar in WT and CCR2^-/- mice. Finally, OVA/OVA CCR2^-/- mice developed increased airway hyper-responsiveness to a degree similar to that in WT mice. We conclude that following repeated airway challenges with Ag in sensitized mice, the development of Th2 responses (elevated IgE, pulmonary eosinophilia, and lung cytokine levels of IL-4 and IL5) and the development of airway hyper-responsiveness are not diminished by a deficiency in CCR2.

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