AMD3100 mobilizes endothelial progenitor cells in mice, but inhibits its biological functions by blocking an autocrine/paracrine regulatory loop of stromal cell derived factor-1 in vitro.
Endothelial progenitor cells (EPCs), a CXCR4-bearing cell line, are thought to positively influence reendothelialization, vascular repair, and angiogenesis. AMD3100, a highly selective antagonist of stromal cell derived factor (SDF)-1 that binds to its receptor, CXCR4, has been shown to induce rapid mobilization of hematopoietic stem cells in mice, dogs, and humans. Results of this study indicate that AMD3100 injection can induce a rapid and potent mobilization of EPCs in mice compared with saline injection. The study demonstrates that murine spleen-derived EPCs can produce high levels of SDF-1 in vitro. Blocking this endogenous SDF-1 with AMD3100 decreases the number of EPCs; inhibits the proliferation, migration, and adhesion of EPCs; and induces EPC apoptosis. In addition, AMD3100 inhibits ectogenous SDF-1alpha induced improvement of EPC functions. However, AMD3100 incubation does not change the functions of CXCR4-negative cell line HPDE6. In conclusion, AMD3100 can be regarded as a potent mobilizer of EPCs in mice. EPCs have an autocrine/paracrine SDF-1 loop, and breaking this loop with AMD3100 can inhibit the EPC functions in vitro.
Institute of Cardiovascular Diseases of PLA, Xin Qiao Hospital of The Third Military Medical University, Chongqing, PR China.
Yangguang
Y
Yin
Lan
L
Huang
Xiaohui
X
Zhao
Yuqiang
Y
Fang
Shiyong
S
Yu
Jinghong
J
Zhao
Bing
B
Cui
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication / Q000187:drug effects; D001596:Benzylamines; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism*; D000080027:Cyclams; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019899:Paracrine Communication / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
D019380:Anti-HIV Agents; D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor