Suppressive effects of recombinant human monokine induced by IFN-gamma (rHuMig) chemokine on the number of committed and primitive hemopoietic progenitors in liquid cultures of CD34+ human bone marrow cells.
Studies in this report investigated potential hemopoietic suppressive effects of human monokine induced by IFN-gamma (HuMig), a CXC chemokine that is chemotactic for activated lymphocytes. rHuMig was purified from Trichoplusia ni cells after infection with a recombinant baculovirus. The recombinant protein was added to liquid cultures of CD34+ human marrow cells stimulated with IL-3 alone or with both IL-3 and either insulin-like growth factor II (IGF-II) or stem cell growth factor (SCF). The number of committed progenitors, colony-forming units for granulocytes and macrophages (CFU-GM), and primitive progenitors, long term culture-initiating cells (LTC-IC) derived from liquid cultures of CD34+ cells, was determined. rHuMig abrogated the IGF-II-dependent enhancement of CFU-GM and long term culture-initiating cell numbers. Additional studies demonstrated that in liquid cultures of CD34+ cells both rHuMig and IFN-inducible protein-10, another CXC chemokine that is related to HuMig, inhibited the production or expansion of CFU-GM. For a subset of marrows, rHuMig also abrogated SCF enhancement of CFU-GM numbers in cultures of CD34+ cells stimulated with both IL-3 and SCF. These studies are the first to demonstrate that rHuMig can act as a negative regulator of in vitro hemopoiesis, that both rHuMig and IP-10 can suppress an increase in the number of committed progenitors from CD34+ cells, and that chemokines can abrogate hemopoietic stimulatory effects of IGF-II.
Schwartz
G N
GN
Department of Experimental Transplantation and Immunology, National Cancer Institute, Bethesda, MD 20892, USA. gns@helix.nih.gov
Liao
F
F
Gress
R E
RE
Farber
J M
JM
D018952:Antigens, CD34; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D054370:Chemokine CXCL9; D018925:Chemokines / Q000494:pharmacology*; D019743:Chemokines, CXC; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins / Q000494:pharmacology
D018952:Antigens, CD34; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins