Deficiency in Fpr2 results in reduced number of Lin-c-Kit+Sca1+ myeloid progenitor cells

Lin-c-Kit+ Sca-1+ cell population in the bone marrow (BM) serves as the direct precursors 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 CD31+Ly6C+ (granulocytes and monocytes), CD31-/Ly6Cint (granuloid cells), and CD31-/Ly6Chigh (predominantly monocytes) cells. In particular, the number of Lin-c-Kit+Sca-1+ (LKS) cells was reduced in Fpr2-/- mouse BM. This was supported by observations of the reduced incorporation of intraperitoneally injected BrdU 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 (Thr308) and Akt (Ser473) 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 Assay revealed that CFU-GM 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+Ly6C+TNF-a+ cells to the spleen of Fpr2-/- mice were significantly reduced. These results demonstrate an important role for Fpr2 in the development of myeloid lineage precursors in mouse BM. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

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