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Induction of Human Monocyte Susceptibility to Lymphokine-activated Killer Cell Lysis by Granulocyte-Macrophage Colony-stimulating Factor¹

University of South Florida College of Medicine, Department of Medical Microbiology & Immunology, Tampa, Florida 33612

We have recently reported that cultured human monocytes are susceptible to lysis by autologous lymphokine-activated killer (LAK) cells. In an attempt to modulate the sensitivity of monocytes to LAK-mediated lysis, monocytes were cultured in the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF was found to enhance the susceptibility of monocytes to lysis by LAK cells by 2- to 5-fold over that of untreated cells in a dose-dependent manner. As little as 10 units of GM-CSF per milliliter was sufficient to induce increased sensitivity. In a kinetics study, susceptibility of monocytes increased after 2 days of incubation with GM-CSF, with peak sensitivity occurring from 4 to 6 days of culture. The effect of GM-CSF appeared to be specific for monocytes within the circulating peripheral blood cells because nonadherent cells (NAC) and granulocytes, which are normally resistant to LAK-mediated lysis, did not become susceptible after treatment with GM-CSF. In cold-target inhibition experiments, unlabeled GM-CSF-treated monocytes, but not untreated monocytes, could block the lysis of FMEX, a human melanoma tumor cell line, as well as freshly isolated tumor cells. Finally, LAK cells specifically bound to GM-CSF-treated monocytes in significantly higher percentages than to control monocytes. In summary, our results indicate that GM-CSF was capable of enhancing the susceptibility of monocytes to LAK lysis possibly via increased binding or expression of target structure(s).

¹ This work was supported in part by NCI Grant CA-46820 and by the American Cancer Society Florida Division Grant No. F888USF-2.

² To whom requests for reprints should be addressed, at University of South Florida College of Medicine, Department of Medical Microbiology & Immunology, Box 10, 12901 North 30th Street, Tampa, FL 33612.

Received 2/21/89. Revised 5/26/89. Accepted 6/20/89.