Work

Deficiency in Fpr2 results in reduced numbers of Lin−cKit+Sca1+ myeloid progenitor cells

Year: 2018

Type: article

Abstract: The Lin − c-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 CD31 + Ly6C + (granulocytes and monocytes), CD31 − /Ly6C int (granuloid cells), and CD31 − /Ly6C high (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 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 + Ly6C + TNFα + 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.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.ra118.002683