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

Keqiang Chen, Vijay K. Singh, Peng Tang, Zhiyao Bao, Tianzhen He, Yi Xiang, Wanghua Gong, Teizo Yoshimura, Yingying Le, Lino Tessarollo, Xin Chen, Ji Ming Wang

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Abstract

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/Ly6Cint (granuloid cells), and CD31/Ly6Chigh (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.

Original languageEnglish
Pages (from-to)13452-13463
Number of pages12
JournalJournal of Biological Chemistry
Volume293
Issue number35
DOIs
Publication statusPublished - Aug 31 2018

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chen, K., Singh, V. K., Tang, P., Bao, Z., He, T., Xiang, Y., Gong, W., Yoshimura, T., Le, Y., Tessarollo, L., Chen, X., & Wang, J. M. (2018). Deficiency in Fpr2 results in reduced numbers of LincKitSca1 myeloid progenitor cells. Journal of Biological Chemistry, 293(35), 13452-13463. https://doi.org/10.1074/jbc.RA118.002683