TY - JOUR
T1 - Deficiency in Fpr2 results in reduced numbers of LincKitSca1 myeloid progenitor cells
AU - Chen, Keqiang
AU - Singh, Vijay K.
AU - Tang, Peng
AU - Bao, Zhiyao
AU - He, Tianzhen
AU - Xiang, Yi
AU - Gong, Wanghua
AU - Yoshimura, Teizo
AU - Le, Yingying
AU - Tessarollo, Lino
AU - Chen, Xin
AU - Wang, Ji Ming
N1 - Funding Information:
This project was funded in part by federal funds from the NCI, National Insti-tutes of Health, under Contract HHSN261200800001E and supported in part by the Intramural Research Program of the NCI, National Institutes of Health. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2018 American Society for Biochemistry and Molecular Biology Inc. All Rights Reserved.
PY - 2018/8/31
Y1 - 2018/8/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85052604502&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052604502&partnerID=8YFLogxK
U2 - 10.1074/jbc.RA118.002683
DO - 10.1074/jbc.RA118.002683
M3 - Article
C2 - 30018139
AN - SCOPUS:85052604502
VL - 293
SP - 13452
EP - 13463
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 35
ER -