The key role of a G protein coupled receptor mFPR2 in the development of inflammatory airway disease (98.4)

Abstract The human G protein-coupled formylpeptide receptor-like 1 (FPRL1) and its mouse homologue mFPR2 mediate leukocyte chemotaxis in response to a variety of chemotactic peptides associated with inflammation and bacterial infection. In order to ascertain the role of this receptor in innate host defense, we generated mFPR2 knockout (mFPR2−/−) mice. mFPR2−/− mice developed normally, but with reduced number of myeloid cells in the bone marrow. In pulmonary allergic inflammation induced by ovalbumin (OVA), mFPR2−/− mice showed markedly reduced myeloid cell exudation in the broncho-alveolar lavage (BAL) and cell infiltration in the lung tissue, in association with impaired epithelial proliferative responses. In addition, the BAL from OVA-treated wild type mice contained high levels of mFPR2 specific chemotactic activity, which was absent in the BAL of mFPR2 −/− mice. Our results indicate a key role for mFPR2 in the development of inflammation in the allergic airway disease. This project has been funded with federal funds from the National Cancer Institutes, National Institutes of Health, under Contract No. NO1-CO-12400 and was also supported in part by the Intramural Research Program of the NCI, NIH.