CC chemokine receptor-2 is not essential for the development of antigen-induced pulmonary eosinophilia and airway hyperresponsiveness

Monocyte chemoattractant proteins-1 and -5 have been implicated as importan t 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 compar ed 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 si gnificant increases in total cells recovered by bronchoalveolar lavage (BAL ) compared with their respective OVA-immunized/PBS-challenged (OVA/PBS) con trol groups. There were no significant differences in BAL cell counts and d ifferentials (i.e., macrophages, PMNs, lymphocytes, and eosinophils) betwee n 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 C CR2(-/-) mice. Lung mRNA expression and BAL cytokine protein levels of IL-4 , IL-5, and IFN-gamma were also similar in WT and CCR2-/- mice. Finally, OV A/OVA CCR2(-/-) mice developed increased airway hyper-responsiveness to a d egree similar to that in WT mice. We conclude that following repeated airwa y 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.