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Human FLT3 ligand acts on myeloid as well as multipotential progenitors derived from purified CD34 + blood progenitors expressing different levels of c‐kit protein
Author(s) -
Sonoda Yoshiaki,
Kimura Takafumi,
Sakabe Hideaki,
Tanimukai Shigeatsu,
Ohmizono Yoshikazu,
Nakagawa Shuichi,
Yokota Shouhei,
Lyman Stewart D.,
Abe Tatsuo
Publication year - 1997
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1997.tb01664.x
Subject(s) - stem cell factor , cd34 , progenitor cell , haematopoiesis , population , microbiology and biotechnology , myeloid , biology , stem cell , interleukin 3 , chemistry , immunology , antigen , medicine , interleukin 21 , environmental health , cd8
Abstract: We studied the effect of human flt3/flk2 ligand (FL) on the proliferation and differentiation of purified CD34 + blood progenitors which express different levels of c‐kit protein in clonal cell culture in comparison with that of stem cell factor (SCF). FL alone did not support significant colony formation. However, FL significantly enhanced neutrophil colony (CFU–G) formation in the presence of granulocyte‐colony stimulating factor (G–CSF) by peripheral blood (PB)‐derived CD34 + c‐kit − cells which contained a large number of CFU–G. In addition, FL could synergistically increase the number of CFU–G supported by a combination of interleukin (IL)‐3 and G–CSF, as did SCF. As we reported previously, SCF showed a significant burst‐promoting activity (BPA). In contrast, FL did not exhibit any BPA on PB‐derived CD34 + c‐kit high cells in which erythroid‐burst (BFU‐E) was highly enriched. However, FL could synergize with IL‐3 or GM–CSF in support of erythrocyte‐containing mixed (E‐Mix) colony by PB‐derived CD34 + c‐kit high or low cells in the presence of Epo. Replating of E‐Mix colonies derived from CD34 + c‐kit high cells supported by IL‐3+Epo+SCF yielded more secondary colonies than those supported by IL‐3+Epo or IL‐3+Epo+FL. When PB‐derived CD34 + c‐kit low cells which represent a more immature population than CD34 + c‐kit high cells were used as the target, number of secondary colonies supported by IL‐3+Epo, IL‐3+Epo+SCF or IL‐3+Epo+FL was comparable. However, the number of lineages expressed in the secondary culture was significantly larger in the primary culture containing IL‐3+Epo+FL than in that containing IL‐3+Epo. These results suggest that FL not only acts on neutrophilic progenitors, but also on more immature multipotential progenitors.