Induction of thymidine kinase activity and clonal growth of certain leukemic cell lines by a granulocyte-derived factor

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.