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Enhancing Effect of Human Monocytic Colony-stimulating Factor on Monocyte Tumoricidal Activity¹

Biochemical Research Laboratory, Morinaga Milk Industry Co., Ltd., 4-22-4, Meguro, Meguro-ku, Tokyo 153 [S. S., H. Y., M. Y., N. Y., M. S., T. K.]; Third Department of Internal Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113 [F. T.]; and Division of Hemopoiesis, Institute of Hematology, Jichi Medical School, Minamikawachi-machi, Kawachi-gun, Tochigi-ken 329-04 [M. S., K. M.]; Japan

Human monocytic colony-stimulating factor (hM-CSF) enhances several effector functions of human peripheral blood monocytes. In this study, we investigated the effect of the M_r 85,000 form of hM-CSF on the tumoricidal activity of human monocytes against several leukemic cell lines using a 12-h chromium release assay. Human peripheral blood monocytes preincubated with hM-CSF for 48 h showed more effective killing activity towards K562, U937, Daudi, and HL60 cells as compared with the cells preincubated with medium alone. Maximal enhancement of the tumoricidal activity was achieved by hM-CSF at concentrations of 50–100 ng/ml. A trace amount of lipopolysaccharide contained in the hM-CSF did not seem to contribute to the enhancing effect, as the addition of a lipopolysaccharide-neutralizing agent, polymyxin B, to the preincubation mixture did not reduce this effect. Anti-tumor necrosis factor antiserum partially blocked the tumoricidal activity mediated by hM-CSF, indicating that tumor necrosis factor may participate in the hM-CSF-mediated increase of monocyte tumor cell-killing activity. These results suggest that in addition to other monocyte-activating factors, hM-CSF augments monocyte tumoricidal activity against a wide spectrum of tumor targets.

¹ This work was supported in part by a grant from the Ministry of Education, Science and Culture, Japan (5027).

² To whom requests for reprints should be addressed.

Received 4/24/89. Revised 7/17/89. Accepted 7/31/89.

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