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Cunningham JM; Purucker ME; Jane SM; Safer B; Vanin EF; Ney PA; Lowrey CH; Nienhuis AW 《Blood》1994,84(4):1298-1308
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FLK-2/FLT-3 ligand regulates the growth of early myeloid progenitors isolated from human fetal liver 总被引:10,自引:5,他引:5
Muench MO; Roncarolo MG; Menon S; Xu Y; Kastelein R; Zurawski S; Hannum CH; Culpepper J; Lee F; Namikawa R 《Blood》1995,85(4):963-972
The effects of the recently identified FLK-2/FLT-3 ligand (FL) on the growth of purified human fetal liver progenitors were investigated under serum-deprived culture conditions. FL alone was found to stimulate modest proliferation in short-term cultures of CD34++ CD38+ lineage (Lin)- light-density fetal liver (LDFL) cells and the more primitive CD34++ CD38- Lin- LDFL cells. However, the low levels of growth induced by FL were insufficient for colony formation in clonal cultures. Synergism between FL and either granulocyte-macrophage colony- stimulating factor (GM-CSF), interleukin-3 (IL-3) or KIT ligand (KL) was observed in promoting the growth of high-proliferative potential (HPP) colony-forming cells (CF) and/or low-proliferative potential (LPP)-CFC in cultures of CD34++ CD38+ Lin- and CD34++ CD38- Lin- LDFL- cells. FL, alone or in combination with other cytokines, was not found to affect the growth of CD34+ Lin- LDFL cells, the most mature subpopulation of fetal liver progenitors investigated. The growth of the most primitive subset of progenitors studied, CD34++ CD38- Lin- LDFL cells, required the interactions of at least two cytokines, because only very low levels of growth were observed in response to either FL, GM-CSF, IL-3 or KL alone. However, the results of delayed cytokine-addition experiments suggested that individually these cytokines did promote the survival of this early population of progenitors. Although two-factor combinations of FL, KL, and GM-CSF were observed to promote the growth of early progenitors in a synergistic manner, neither of these factors was found to make fetal liver progenitors more responsive to suboptimal concentrations of a second cytokine. Only myeloid cells were recovered from liquid cultures of CD34++ CD38- Lin- LDFL cells grown in the presence of combinations of FL, KL, and GM-CSF. These results indicate that FL is part of a network of growth factors that regulate the growth and survival of early hematopoietic progenitors. 相似文献
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The attachment of particle-bound IgG in a nonphagocytic system stimulates formation of a microfilament-rich, organelle-poor zone in the subjacent cytoplasm of human neutrophils. The attachment site is characterized by ruffling and invagination of the neutrophil membrane. Both IgG attachment and formation of the organelle-poor zone are inhibited by the microfilament inhibitor cytochalasin-B, but not by inhibitors of microtubules, such as colchicine or vinca alkaloids. In contrast, attachment of particle-bound complement is not inhibited by cytochalasin-B in doses known to disrupt actin filaments. There is no discernable change in the subjacent cytoplasm of the neutrophil in response to complement and the membrane attachment site is smooth, without ruffling or invagination. These studies disclose that both IgG- mediated attachment to neutrophils and its sequel, peripheral cytoplasmic reorganization, are mediated by cytochalasin-sensitive structures, possibly actin. Complement-mediated attachment to neutrophils is insensitive to high doses of cytochalasin, suggesting that actin integrity is not required. 相似文献