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Induction of thymidine kinase activity and clonal growth of certain
leukemic cell lines by a granulocyte-derived factor
CK Ho, BR Ou, ML Hsu, SN Su, CH Yung and SY Wang
Department of Medical Research, Veterans General Hospital, Taipei, Taiwan,
Republic of China.
Normal polymorphonuclear neutrophils (PMNs) constitutively secrete a
mediator designated granulocyte-derived factor (GDF) that can enhance the
uptake of 3H-thymidine (3- to 20-fold) by the molt-3, CTV-1, and K562
leukemic cell lines in a dose-dependent manner. GDF is heat labile (56
degrees C for 30 minutes) and acid labile (pH 2.0) and is sensitive to
treatment with bacterial protease type IV. Our preliminary studies suggest
that GDF is non-dialyzable (molecular weight cutoff, 12,000), binds to
diethylaminoethyl (DEAE), and has an apparent molecular weight (mol wt) of
about 40 Kd. Production of GDF is unaffected by treatment of PMN with
activating agents (interferon gamma, OK432, phorbol ester, calcium
ionophore, poly I:C) or metabolic inhibitors (actinomycin-D and
cyclohexamide), suggesting that GDF is constitutively secreted. Despite the
marked enhancement of 3H-thymidine uptake, cell number and the rate of DNA
synthesis in GDF responsive cultures remain unchanged. In contrast, the
clonogenic efficiency of the responsive cells is greatly increased in the
presence of GDF. These phenomena occur in parallel to an amplification of
the level of thymidine kinase activity in the sensitive cells. GDF is
distinct from a panel of different lymphokines and monokines in
antigenicity and biochemical and functional characteristics, and is
possibly a novel cytokine that can alter the pattern of DNA synthesis and
growth characteristics of certain hematopoietic cells. However, its
biologic and physiologic significance remains to be determined.
Volume 75,
Issue 12,
pp. 2438-2444,
06/15/1990
Copyright © 1990 by The American Society of Hematology

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