Deficiency in Fpr2 results in reduced numbers of LincKitSca1 myeloid progenitor cells

The Linc-Kit Sca-1 cell population in the bone marrow (BM) serves as the direct precursor for differentiation of myeloid cells. In this study, we report that deficiency in Fpr2, a G protein– coupled chemoattractant receptor in mice, is associated with reduced BM nucleated cells, including CD31Ly6C (granulocytes and monocytes), CD31/Ly6C^int (granuloid cells), and CD31/Ly6C^high (predominantly monocytes) cells. In particular, the number of Linc-KitSca-1 (LKS) cells was reduced in Fpr2/ mouse BM. This was supported by observations of the reduced incorporation of intraperitoneally injected bromodeoxyuridine by cells in the c-Kit population from Fpr2/ mouse BM. Purified c-Kit cells from Fpr2/ mice showed reduced expansion when cultured in vitro with stem cell factor (SCF). SCF/c-Kit-mediated phosphorylation of P38, STAT1, Akt (Thr-308), and Akt (Ser-473) was also significantly reduced in c-Kit cells from Fpr2/ mice. Furthermore, Fpr2 agonists enhanced SCF-induced proliferation of c-Kit cells. Colony-forming unit assays revealed that CFU– granulocyte–macrophage formation of BM cells from Fpr2/ mice was significantly reduced. After heat-inactivated bacterial stimulation in the airway, the expansion of c-kit Sca-1 cells in BM and recruitment of Ly6G cells to the lungs and CD11b Ly6CTNF cells to the spleen of Fpr2/ mice was significantly reduced. These results demonstrate an important role for Fpr2 in the development of myeloid lineage precursors in mouse BM.