PMID- 11940331
OWN - NLM
STAT- MEDLINE
DCOM- 20020419
LR  - 20131121
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 115
IP  - 2
DP  - 2002 Feb
TI  - Recombinant human Flt3 ligand exerts both direct and indirect effects on 
      hematopoiesis.
PG  - 202-5
AB  - OBJECTIVE: To investigate the direct effects of the Flt3 ligand (FL) on 
      hematopoiesis, such as the stimulation of the formation of hematopoietic colonies 
      and the proliferation of dendritic cells, as well as the indirect stimulation of 
      hematopoiesis, especially via the proliferation of endothelial cells. METHODS: 
      Mononuclear cells from human cord blood were plated in methylcellulose medium 
      containing different cytokines to induce hematopoietic colony formation. 
      Dendritic cells (DCs) were induced from the mononuclear cells with a cytokine 
      cocktail with or without recombinant human soluble FL (rhFL; 100 ng/ml). The Flt3 
      receptors on the surface of a human microvascular endothelial cell line (ECV) 
      were analyzed by flow cytometry. The proliferation of ECV stimulated by rhFL was 
      measured with the microculture tetrazolium assay. The levels of FL, IL-6, IL-8, 
      G-CSF and GM-CSF in the supernatant of ECV cultures were measured by enzyme 
      linked immunoabsorbent assay (ELISA). RESULTS: rhFL stimulates colony formation 
      from cord blood when used as a sole stimulant. FL in combination with other 
      cytokines increased colony formation significantly. The number of DCs was 
      approximately 2.5 times higher when rhFL was used. rhFL stimulates the 
      proliferation of ECV on which Flt3 receptors are expressed. Furthermore, ECV 
      secretes FL, IL-6, IL-8, G-CSF and GM-CSF, which were augmented by tumor necrosis 
      factor-alpha and rhFL. CONCLUSIONS: rhFL enhances hematopoietic colony formation 
      and DC proliferation from human cord blood cells. FL not only stimulates the 
      proliferation of ECV, but is also secreted by ECV. FL may exert direct and 
      indirect effects on hematopoiesis.
FAU - Xu, Zhixiang
AU  - Xu Z
AD  - Department of Immunology, Medical Biotechnology Institute, Suzhou Medical 
      College, Suzhou 215007, China.
FAU - Xu, Ying
AU  - Xu Y
FAU - Zhu, Jiankun
AU  - Zhu J
FAU - Shi, Qin
AU  - Shi Q
FAU - Li, Ying
AU  - Li Y
FAU - Zhang, Xueguang
AU  - Zhang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (flt3 ligand protein)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Dendritic Cells/cytology/drug effects/immunology
MH  - Dexamethasone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/cytology/drug effects/metabolism
MH  - Fetal Blood/cytology/drug effects
MH  - Hematopoiesis/*drug effects
MH  - Hematopoietic Stem Cells/cytology/drug effects
MH  - Humans
MH  - Immunophenotyping
MH  - Membrane Proteins/*pharmacology
MH  - Recombinant Proteins/*pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2002/04/10 10:00
MHDA- 2002/04/20 10:01
CRDT- 2002/04/10 10:00
PHST- 2002/04/10 10:00 [pubmed]
PHST- 2002/04/20 10:01 [medline]
PHST- 2002/04/10 10:00 [entrez]
PST - ppublish
SO  - Chin Med J (Engl). 2002 Feb;115(2):202-5.